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RecruitingInterventionalPhase 3

A Phase III, Randomized Study of Daratumumab, Cyclophosphamide, Bortezomib and Dexamethasone (Dara-VCD) Induction Followed by Autologous Stem Cell Transplant or Dara-VCD Consolidation and Daratumumab Maintenance in Patients With Newly Diagnosed AL Amyloidosis

NCT ID: NCT06022939Sponsor: SWOG Cancer Research NetworkLast updated: 2026-05-06

Summary

This phase III trial compares the effect of adding a stem cell transplant with melphalan after completing chemotherapy with daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) versus chemotherapy with Dara-VCD alone for treating patients with newly diagnosed amyloid light chain (AL) amyloidosis. Melphalan is a chemotherapy given prior to a stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. The stem cells are then returned to the patients to replace the blood forming cells that were destroyed by the chemotherapy. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs, such as cyclophosphamide and bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to lower the body's immune response to help stop the growth of cancer cells. Giving a stem cell transplant with melphalan after Dara-VCD may kill more cancer cells in patients with newly diagnosed AL amyloidosis.

Detailed description

PRIMARY OBJECTIVE: I. To compare major organ deterioration progression-free survival between participants randomized to the autologous stem cell transplant (ASCT) and non-ASCT arms of this study. SECONDARY OBJECTIVES: I. To compare overall survival (OS) between participants randomized to the ASCT and non-ASCT arms of this study. II. To compare rates of cardiac and renal organ responses between participants randomized to the ASCT and non-ASCT arms of this study. III. To compare rates of cardiac and renal organ progression between participants randomized to the ASCT and non-ASCT arms of the study. IV. To compare the frequency and severity of toxicities between participants randomized to the ASCT and non-ASCT arms of this study. V. To compare minimal residual disease (MRD) negativity rates between participants randomized to the ASCT and non-ACST arms of this study. ADDITIONAL OBJECTIVES: I. To compare the best overall hematologic response rates between participants randomized to the ASCT and non-ASCT arms of this study. II. To compare rates of hematologic complete response (CR) and very good partial response, following completion of consolidation therapy between participants randomized to the ASCT and non-ASCT arms of this study, post-consolidation. III. To compare hematologic progression-free survival between participants randomized to the ASCT and non-ASCT arms of this study. IV. To compare time to next treatment between participants randomized to the ASCT and non-ASCT arms of the study. V. To evaluate utilization of delayed ASCT in participants randomized to the non-ASCT arm of the study. TRANSLATIONAL MEDICINE PRIMARY OBJECTIVES: I. To compare MRD negativity rates from bone marrow aspirates via next generation flow cytometry (NGF) between the ASCT and non-ASCT arms of this study post-consolidation. II. To bank specimens for future use. TRANSLATIONAL MEDICINE EXPLORATORY OBJECTIVES: I. To evaluate MRD negativity rates at post-induction, and compare MRD negativity rates at 12 months post-consolidation from bone marrow aspirates via NGF between participants randomized to the ASCT and non-ASCT arms of this study. II. To investigate the association of achieving MRD negativity at any point (post-induction, post-consolidation, or 12 months post-consolidation) via NGF from bone marrow aspirates with major organ deterioration-progression free survival (MOD-PFS). III. To investigate the association of achieving sustained MRD negativity (MRD negative at two consecutive measurements -- post-induction, post-consolidation, and 12 months post-consolidation) via NGF from bone marrow aspirates with MOD-PFS. QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE: I. To compare patient-reported physical function following consolidation treatment between participants randomized to the ASCT and non-ASCT arms using the Patient Reported Outcomes Measurement Information System (PROMIS)-29+2 Profile version (v) 2.1 physical function sub-scale. QOL SECONDARY OBJECTIVES: I. To compare patient-reported fatigue following consolidation treatment between participants randomized to the ASCT and non-ASCT arms using the PROMIS-29 fatigue subscale. II. To compare longitudinal changes in physical function using the PROMS-29+2 between participants randomized to the ASCT and non-ASCT arms. QOL EXPLORATORY OBJECTIVES: I. To assess baseline symptom burden in AL amyloidosis patients prior to induction therapy using the PROMIS-29+2. II. To compare mean scores of symptom scales using the PROMIS-29+2 following consolidation treatment, and at 6 months and 12 months from step 3 registration between treatment arms. III. To compare mean scores of functional scales using the PROMIS-29+2, following consolidation treatment, and at 6 months and 12 months from step 3 registration between treatment arms. IV. To explore whether longitudinal changes in symptoms, functioning, and overall heath related quality of life (HRQoL) as assessed by the PROMIS-29 +2 (version 2.1) differ according to treatment group and, separately, according to baseline cardiac or renal involvement using interaction tests between participants randomized to the ASCT and non-ASCT arms. V. To compare health utility indices using the PROMIS preference score (PROPr) between patients randomized to the ASCT and non-ASCT arms. PATIENT REPORTED OUTCOME (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) PRIMARY OBJECTIVE: I. To compare patient reported symptoms regarding treatment emergent adverse events of interest using the Patient Reported Outcome CTCAE (PRO-CTCAE) Measurement System between patients randomized to the ASCT and non-ASCT arms of this study. OUTLINE: INDUCTION: Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) over 3-5 minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients receive bortezomib SC over 3-5 minutes, cyclophosphamide orally (PO) or intravenously (IV), and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)-CT and fat pad aspiration at screening. Patients undergo echocardiography at screening, the completion of induction, and at progression. Patients undergo bone marrow aspiration and biopsy at screening, post induction treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression. CONSOLIDATION: Patients who achieve an overall response of partial response or better after 3 cycles of Dara-VCD are randomized to 1 of 2 arms. ARM I: Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and 15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within14-28 days post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression. ARM II: Patients undergo collection of peripheral blood stem cells. Patients receive melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90 days post initiation of stem cell transplant. Patients undergo blood and urine sample collection at screening, during treatment, and the end of treatment and during follow up or at progression. MAINTENANCE: Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5 minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening, 12 months post consolidation treatment and at progression. Patients undergo bone marrow aspiration and biopsy 12 months post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, during treatment, 12 months post consolidation treatment and during follow up or at progression. After completion of study treatment, patients are followed up every 3 or 6 months up to 4 years after registration.

Arms & interventions

  • ProcedureAutologous Hematopoietic Stem Cell Transplantation

    Given IV

  • ProcedureBiopsy

    Undergo fat pad biopsy

  • ProcedureBiospecimen Collection

    Undergo blood and urine specimen collection

  • ProcedureBone Marrow Aspiration

    Undergo bone marrow aspiration

  • ProcedureBone Marrow Biopsy

    Undergo bone marrow biopsy

  • DrugBortezomib

    Given SC

  • ProcedureComputed Tomography

    Undergo CT scan

  • DrugCyclophosphamide

    Given PO or IV

  • DrugDaratumumab and Hyaluronidase-fihj

    Given SC

  • DrugDexamethasone

    Given PO or IV

  • ProcedureEchocardiography

    Undergo echocardiography

  • ProcedureMagnetic Resonance Imaging

    Undergo MRI

  • DrugMelphalan

    Given IV

  • ProcedurePositron Emission Tomography

    Undergo PET-CT

  • ProcedureStem Cell Isolation

    Undergo stem cell collection

  • OtherSurvey Administration

    Ancillary study

Outcome measures

Primary

  • Major organ deterioration progression-free survival (PFS)

    Will be performed using a stratified log-rank test for comparison between study arms. The analyses will be stratified according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 versus \[vs.\] 2-3), hematological response following 2 cycles of daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) induction (partial response \[PR\] or worse vs. very good partial response \[VGPR\] or better), and presence of t(11;14) by interphase fluorescence in situ hybridization \[iFISH\] (yes vs. no). All eligible participants will be considered in analyses of the primary endpoint, according to their assigned arm at randomization.

    Time frame: From date of randomization (Step 2 registration) to date of first documentation of hematologic progression, cardiac organ progression, renal organ progression, or death due to any cause, assessed up to 4 years

Secondary

  • Overall survival

    Time frame: From randomization to date of death due to any cause, assessed up to 4 years

  • Hematologic PFS

    Time frame: From randomization (Step 2 registration) to date of first documentation of hematologic progression, or death due to any cause, assessed up to 4 years

  • Cardiac and renal organ response rates

    Time frame: Up to 4 years

  • Measurable residual disease (MRD) negativity rate

    Time frame: From baseline to off treatment follow-up (prior to progression) or 12 months post consolidation

  • Best overall hematologic response

    Time frame: From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years

  • Overall hematologic response rate

    Time frame: From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years

  • Rate of complete response

    Time frame: Up to 4 years

  • Rate of very good complete response or better

    Time frame: Up to 4 years

  • Time to next treatment

    Time frame: From date of initial registration (Step 1) to date of initiation of next line of therapy, assessed up to 4 years

  • Change in patient reported health quality of life (QOL)

    Time frame: From baseline to post-maintenance, approximately 24 months

  • Incidence of adverse events

    Time frame: Up to the end of maintenance therapy, approximately 24 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * STEP 1: Participants must have systemic AL amyloidosis which is biopsy proven and includes histologically-confirmed by positive Congo red stain with green birefringence on polarized light microscopy, OR characteristic appearance by electron microscopy AND confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or immunofluorescence). If there is question regarding diagnosis, consult study chairs prior to registration * STEP 1: Participants must have measurable disease within 28 days prior to treatment if initiated prior to registration or within 28 days of registration as defined by at least one of the following: * Positive monoclonal serum immunofixation electrophoresis * Positive monoclonal urine immunofixation electrophoresis * Monoclonal plasma cells in bone marrow In addition, participants must also have a difference between the involved and uninvolved free light chain (dFLC) \>= 2 mg/dL * STEP 1: Participants may receive up to one cycle (or 28 days) of therapy prior to enrollment. If a patient receives \>= 75% of 1 cycle of protocol identical Dara-VCD, this will be considered 1 cycle of protocol induction. Any patient who receives less than 75% of 1 cycle of Dara-VCD or non-protocol therapy will still be eligible but will be treated per protocol. If protocol identical therapy is initiated prior to enrollment, this treatment is not continued but rather treatment is dictated per protocol * STEP 1: Participants may be receiving chronic corticosteroids if they are being given for disorders other than AL amyloidosis or myeloma * STEP 1: Participant must be \>= 18 years old * STEP 1: Participant must have Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0, 1, or 2 (PS = 3 may be allowed if secondary to neuropathy) * STEP 1: Participant must have a complete medical history and physical exam within 28 DAYS prior to registration * STEP 1: Participants must be willing to undergo high dose chemotherapy and autologous stem cell transplantation if they are randomized to the arm receiving high dose chemotherapy and autologous stem cell transplantation * STEP 1: Participants must be eligible to receive high dose chemotherapy with melphalan at a dose of 200 mg/m\^2 or 140 mg/m\^2 (200 mg/m\^2 is highly encouraged but not mandated). Transplant eligibility criteria are included in the general eligibility criteria listed below: * Participant must have a supine systolic blood pressure (BP) \>= 90 mmHg (at registration step-1, this may by supported by midodrine * Participant must have non-severe cardiac AL (meeting all the below criteria) as defined by: * N-terminal proB-type natriuretic peptide (NT proBNP) \< 5000 (if no NTproBNP, brain natriuretic peptide \[BNP\] must be available and \< 400) * Troponin T (TnT) \< 0.06. If not available, one of the following two criteria must be met: * High sensitivity troponin (hsTnT) T \< 75 or troponin I \< 0.1ng/dL * New York Heart Association (NYHA) I or II * Cardiac ejection fraction (EF) \>= 40% * STEP 1: Hemoglobin \>= 8.0 g/dL (\> 5 mmol/L); red blood cell transfusion allowed up to 7 day prior to registration (within 28 days prior to registration) (NOTE: Growth factor support granulocyte colony-stimulating factor \[G-CSF\] is permitted per institutional guidelines) * STEP 1: Leukocytes \>= 2 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 1: Absolute neutrophil count \>= 1.0 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 1: Platelets \>= 50 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 1: Total bilirubin =\< 1.5 times the institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN (within 28 days prior to registration) * STEP 1: Direct bilirubin =\< 2.0 mg/dL (within 28 days prior to registration) * STEP 1: Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =\< 3x upper limit of normal (ULN) (except if secondary to hepatic involvement) (within 28 days prior to registration) * STEP 1: Alkaline phosphatase =\< 750 U/L (except if secondary to hepatic involvement) (within 28 days prior to registration) * STEP 1: Participants must have a serum creatinine =\< the institutional (I)ULN OR measured OR calculated creatinine clearance \>= 30 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to registration * STEP 1: If peripheral neuropathy is present at diagnosis, participants must be grade 2 (moderate symptoms; limiting instrumental activity of daily living \[ADL\]) or less * STEP 1: Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better * STEP 1: Participants must not be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR * STEP 1: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated * STEP 1: Participants must not have concurrent multiple myeloma as defined by the presence of lytic bone disease, plasmacytomas, \>= 60% plasma cells in the bone marrow, or hypercalcemia. Participants will not be excluded solely based on the presence of plasma cells \> 10% in the bone marrow unless the plasma cell percentage exceeds \>60% * STEP 1: Participants must not have known allergies to any of the study drugs * STEP 1: Participants must not have had a major surgery within 14 days prior to registration and be fully recovered from surgery completed within 14 days prior to registration * STEP 1: Participants must not have a known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal * STEP 1: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration * STEP 1: Participants must not have either moderate or severe persistent asthma within the past 2 years), or currently have uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study) * STEP 1: Participants must not have uncontrolled diabetes within 28 days prior to registration * STEP 1: Participants must not have uncontrolled blood pressure and hypertension within 14 days prior to registration. Participants must have a supine systolic BP of \>= 90 mmHg * STEP 1: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen * STEP 1: Participants must not have received vaccination with live attenuated vaccines within 28 days prior to Registration to Step 1 * STEP 1: Participants must not have uncontrolled infection at the discretion of the enrolling physician and to be discussed with the study chair if the participant is on active anti-infectious therapy. Any patient on active anti-microbial therapy for chronic infectious issues should be discussed with the study chair prior to enrollment * STEP 1: Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen * STEP 1: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwestern Oncology group (SWOG) Specimen Tracking System * STEP 1: Participants must agree to have blood, bone marrow core biopsy and aspirate, and fat pad biopsy specimens submitted for minimal residual disease assessment and future exploratory studies * STEP 1: Participants who can complete PRO, QOL, PRO-CTCAE questionnaires, etc. forms in English, Spanish and French must participate in the patient-reported outcomes and quality of life * STEP 2: Participants must have met all eligibility criteria for Step-1 registration * STEP 2: Participants must have achieved at least a partial response * STEP 2: Participants must continue receiving at least one of study drugs (bortezomib, cyclophosphamide, or daratumumab and hyaluronidase-fihj) if another study drug (daratumumab and hyaluronidase-fihj, cyclophosphamide, or bortezomib) has been discontinued due to adverse events. Note: daratumumab and hyaluronidase-fihj cannot be permanently discontinued * STEP 2: Participants must have completed induction therapy * STEP 2: Participants must be registered to Step 2 within 42 days of cycle 3, day 28 of induction therapy * STEP 2: Participants must plan to initiate their assigned consolidation therapy within 8 weeks after randomization * STEP 2: Participants must not have experienced a MOD-PFS event * STEP 2: Participants must have ECOG performance score (PS) of 0, 1, or 2 (PS = 3 may be allowed if secondary to neuropathy) * STEP 2: Participant must have a complete medical history and physical exam within 28 days prior to registration * STEP 2: Participants must be willing to undergo high dose chemotherapy and autologous stem cell transplantation if they are randomized to the arm receiving high dose chemotherapy and autologous stem cell transplantation * STEP 2: Participants randomized to Arm 2 must be willing and able to return to a participating treatment center for their assigned treatment after transplant. Note that participants need not to have a direct relationship with the transplant center in order to register * STEP 2: Participants must be eligible to receive high dose chemotherapy with melphalan at a dose of 200 mg/m\^2 or 140 mg/m\^2 (200 mg/m\^2 is highly encouraged but not mandated). Transplant eligibility criteria are included in the general eligibility criteria listed below: * Patient must have a supine systolic BP \>= 90 mmHg (at registration step-1, this may not by supported by midodrine) * Patient must have non-severe cardiac AL as defined by: * NT proBNP \<5000 (if no NTproBNP, BNP must be available and \< 400 pg/mL) (within 14 days prior to registration step-2) * TnT \< 0.06. If not available, one of the following two criteria must be met (within 14 days prior to registration step-2) * hsTnT \<75 or troponin I \< 0.1ng/dL * NYHA I or II (within 14 days prior to registration step-2) * Cardiac EF \>= 40% (within 14 days prior to registration step-2) * STEP 2: Hemoglobin \> 8.0 g/dL (\> 5 mmol/L); red blood cell transfusion allowed up to 7 days prior to registration (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 2: Leukocytes \>= 2 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 2: Absolute neutrophil count \>= 1.0 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 2: Platelets \>= 50 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 2: Total bilirubin =\< 1.5 times the institutional ULN unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN (within 28 days prior to registration) * STEP 2: Direct bilirubin =\< 2.0 mg/dL (except if secondary to hepatic involvement) (within 28 days prior to registration) * STEP 2: AST/ALT =\< 3x upper limit of normal (ULN) (except if secondary to hepatic involvement) (within 28 days prior to registration) * STEP 2: Alkaline phosphatase =\< 750 U/L (except if secondary to hepatic involvement) (within 28 days prior to registration) * STEP 2: Participants must have a serum creatinine =\< the IULN OR calculated creatinine clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration * STEP 2: Participants must not have uncontrolled infection at the discretion of the enrolling physician and to be discussed with the study chair if the participant is on active anti-infectious therapy. Any patient on active anti-microbial therapy for chronic infectious issues should be discussed with the study chair prior to enrollment * STEP 2: Participants randomized to the ASCT arm must be able to have at least 2.0 x 10\^6 CD34 cells/kg collected * STEP 2: Participants who can complete PRO, QOL, PRO-CTCAE questionnaires, etc. forms in English, Spanish and French must participate in the patient-reported outcomes and quality of life * STEP 3: Participants must have met all eligibility criteria for Step-1 and Step-2 registration * STEP 3: Participants must not have had daratumumab and hyaluronidase-fihj permanently discontinued during induction or consolidation * STEP 3: Participants must have completed induction and consolidation therapy * STEP 3: Participants must be registered to Step 3 within the following time frames: * If randomized to Arm 1 Dara-VCD consolidation: within 28 days of completion of 3 cycles of consolidation therapy * If randomized to Arm 2 high dose chemotherapy and autologous stem cell transplantation: within 180 days following initiation of stem cell transplantation * STEP 3: Participants must not have experienced a MOD-PFS event * STEP 3: Participants must have ECOG performance score (PS) of 0, 1, or 2 (PS = 3 is allowed if secondary to neuropathy) * STEP 3: Participants must have a complete medical history and physical exam within 28 DAYS prior to registration * STEP 3: Hemoglobin \> 8.0 g/dL (\> 5 mmol/L); red blood cell transfusion allowed up to 7 days prior to registration (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 3: Leukocytes \>= 2 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 3: Absolute neutrophil count \>= 1.0 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 3: Platelets \>= 50 x 10\^3/uL (within 28 days prior to registration) (NOTE: Growth factor support \[G-CSF\] is permitted per institutional guidelines) * STEP 3: Total bilirubin =\< 1.5 times the institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN (within 28 days prior to registration) * STEP 3: Direct bilirubin =\< 2.0 mg/dL (within 28 days prior to registration) * STEP 3: AST/ALT =\< 3x upper limit of normal (ULN) (except if secondary to hepatic involvement) (within 28 days prior to registration) * STEP 3: Alkaline phosphatase =\< 750 U/L (except if secondary to hepatic involvement) (within 28 days prior to registration) * STEP 3: Participants must not have uncontrolled infection at the discretion of the enrolling physician and to be discussed with the study chair if the participant is on active anti-infectious therapy. Any patient on active anti-microbial therapy for chronic infectious issues should be discussed with the study chair prior to enrollment * Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

Study locations (117)

CTCA at Western Regional Medical Center

Goodyear, Arizona, 85338

Recruiting
Site Public Contact · Contact
Tibor J. Kovacsovics · Principal Investigator

Banner University Medical Center - Tucson

Tucson, Arizona, 85719

Recruiting
Site Public Contact · Contact
Muhammad Husnain · Principal Investigator

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719

Recruiting
Site Public Contact · Contact
Muhammad Husnain · Principal Investigator

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

Recruiting
Site Public Contact · Contact
Michael A. Rosenzweig · Principal Investigator

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612

Recruiting
Site Public Contact · Contact
Polina Bellman · Principal Investigator

City of Hope at Irvine Lennar

Irvine, California, 92618

Recruiting
Site Public Contact · Contact
Michael A. Rosenzweig · Principal Investigator

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868

Recruiting
Site Public Contact · Contact
Polina Bellman · Principal Investigator

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, 06830

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

Yale University

New Haven, Connecticut, 06520

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, 06902

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611

Recruiting
Site Public Contact · Contact
Terri L. Parker · Principal Investigator

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007

Recruiting
Site Public Contact · Contact
Kimberley Doucette · Principal Investigator

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

UM Sylvester Comprehensive Cancer Center at Coral Springs

Coral Springs, Florida, 33065

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida, 33021

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

North Miami, Florida, 33181

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324

Recruiting
Site Public Contact · Contact
James E. Hoffman · Principal Investigator

Emory University Hospital Midtown

Atlanta, Georgia, 30308

Recruiting
Site Public Contact · Contact
Jonathan L. Kaufman · Principal Investigator

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322

Recruiting
Site Public Contact · Contact
Jonathan L. Kaufman · Principal Investigator

Rush-Copley Medical Center

Aurora, Illinois, 60504

Recruiting
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Priyank P. Patel · Principal Investigator

University of Illinois

Chicago, Illinois, 60612

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Ana Maria Avila Rodriguez · Principal Investigator

Carle at The Riverfront

Danville, Illinois, 61832

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Priyank P. Patel · Principal Investigator

Carle Physician Group-Effingham

Effingham, Illinois, 62401

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Site Public Contact · Contact
Priyank P. Patel · Principal Investigator

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938

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Priyank P. Patel · Principal Investigator

Loyola University Medical Center

Maywood, Illinois, 60153

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Patrick A. Hagen · Principal Investigator

Carle Cancer Center

Urbana, Illinois, 61801

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Priyank P. Patel · Principal Investigator

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, 50023

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Seema Harichand-Herdt · Principal Investigator

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, 50325

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Seema Harichand-Herdt · Principal Investigator

Iowa Methodist Medical Center

Des Moines, Iowa, 50309

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Seema Harichand-Herdt · Principal Investigator

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, 50309

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Seema Harichand-Herdt · Principal Investigator

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, 50314

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Seema Harichand-Herdt · Principal Investigator

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa, 50263

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Seema Harichand-Herdt · Principal Investigator

University of Kansas Cancer Center

Kansas City, Kansas, 66160

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Muhammad Umair Mushtaq · Principal Investigator

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205

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Muhammad Umair Mushtaq · Principal Investigator

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600

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Christin Destefano · Principal Investigator

Boston Medical Center

Boston, Massachusetts, 02118

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Vaishali Sanchorawala · Principal Investigator

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109

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Matthew J. Pianko · Principal Investigator

Henry Ford Cancer Institute-Downriver

Brownstown, Michigan, 48183

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Philip Kuriakose · Principal Investigator

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, 48038

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Philip Kuriakose · Principal Investigator

Henry Ford Medical Center-Fairlane

Dearborn, Michigan, 48126

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Philip Kuriakose · Principal Investigator

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201

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Andrew Kin · Principal Investigator

Henry Ford Hospital

Detroit, Michigan, 48202

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Philip Kuriakose · Principal Investigator

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334

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Andrew Kin · Principal Investigator

Allegiance Health

Jackson, Michigan, 49201

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Philip Kuriakose · Principal Investigator

Karmanos Cancer Institute at McLaren Greater Lansing

Lansing, Michigan, 48910

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Andrew Kin · Principal Investigator

Henry Ford Medical Center-Columbus

Novi, Michigan, 48377

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Philip Kuriakose · Principal Investigator

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322

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Philip Kuriakose · Principal Investigator

Henry Ford Wyandotte Hospital

Wyandotte, Michigan, 48192

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Philip Kuriakose · Principal Investigator

Mercy Hospital

Coon Rapids, Minnesota, 55433

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David M. King · Principal Investigator

Fairview Southdale Hospital

Edina, Minnesota, 55435

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Site Public Contact · Contact
David M. King · Principal Investigator

Abbott-Northwestern Hospital

Minneapolis, Minnesota, 55407

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Site Public Contact · Contact
David M. King · Principal Investigator

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

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Taxiarchis Kourelis · Principal Investigator

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, 55416

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David M. King · Principal Investigator

Regions Hospital

Saint Paul, Minnesota, 55101

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David M. King · Principal Investigator

United Hospital

Saint Paul, Minnesota, 55102

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Site Public Contact · Contact
David M. King · Principal Investigator

Baptist Memorial Hospital and Cancer Center-Oxford

Oxford, Mississippi, 38655

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Brion V. Randolph · Principal Investigator

Baptist Memorial Hospital and Cancer Center-Desoto

Southhaven, Mississippi, 38671

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Brion V. Randolph · Principal Investigator

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376

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Keith E. Stockerl-Goldstein · Principal Investigator

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141

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Keith E. Stockerl-Goldstein · Principal Investigator

Washington University School of Medicine

St Louis, Missouri, 63110

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Keith E. Stockerl-Goldstein · Principal Investigator

Siteman Cancer Center-South County

St Louis, Missouri, 63129

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Keith E. Stockerl-Goldstein · Principal Investigator

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136

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Keith E. Stockerl-Goldstein · Principal Investigator

Nebraska Medicine-Bellevue

Bellevue, Nebraska, 68123

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Sarah A. Holstein · Principal Investigator

Nebraska Medicine-Village Pointe

Omaha, Nebraska, 68118

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Sarah A. Holstein · Principal Investigator

University of Nebraska Medical Center

Omaha, Nebraska, 68198

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Sarah A. Holstein · Principal Investigator

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748

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Heather J. Landau · Principal Investigator

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645

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Heather J. Landau · Principal Investigator

Memorial Sloan Kettering Commack

Commack, New York, 11725

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Heather J. Landau · Principal Investigator

Memorial Sloan Kettering Westchester

Harrison, New York, 10604

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Heather J. Landau · Principal Investigator

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032

Recruiting
Rajshekhar Chakraborty · Principal Investigator

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

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Heather J. Landau · Principal Investigator

University of Rochester

Rochester, New York, 14642

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Frank C. Passero · Principal Investigator

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204

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Raymond Thertulien · Principal Investigator

Duke University Medical Center

Durham, North Carolina, 27710

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Cristiana C. Chase · Principal Investigator

Novant Health Cancer Institute - Huntersville

Huntersville, North Carolina, 28078

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Raymond Thertulien · Principal Investigator

Novant Health Cancer Institute - Mooresville

Mooresville, North Carolina, 28117

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Raymond Thertulien · Principal Investigator

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, 27103

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Franklin L. Chen · Principal Investigator

Case Western Reserve University

Cleveland, Ohio, 44106

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Timothy E. O'brien · Principal Investigator

Riverside Methodist Hospital

Columbus, Ohio, 43214

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Yvonne A. Efebera · Principal Investigator

Providence Newberg Medical Center

Newberg, Oregon, 97132

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Charles W. Drescher · Principal Investigator

Providence Willamette Falls Medical Center

Oregon City, Oregon, 97045

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Charles W. Drescher · Principal Investigator

Providence Portland Medical Center

Portland, Oregon, 97213

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Charles W. Drescher · Principal Investigator

Providence Saint Vincent Medical Center

Portland, Oregon, 97225

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Charles W. Drescher · Principal Investigator

Oregon Health and Science University

Portland, Oregon, 97239

Active Not Recruiting

Geisinger Medical Center

Danville, Pennsylvania, 17822

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Joseph P. Lynch · Principal Investigator

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

Recruiting
Adam Waxman · Principal Investigator

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107

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Adam F. Binder · Principal Investigator

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, 18711

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Joseph P. Lynch · Principal Investigator

Baptist Memorial Hospital and Cancer Center-Collierville

Collierville, Tennessee, 38017

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Brion V. Randolph · Principal Investigator

Baptist Memorial Hospital and Cancer Center-Memphis

Memphis, Tennessee, 38120

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Site Public Contact · Contact
Brion V. Randolph · Principal Investigator

Houston Methodist San Jacinto Hospital

Baytown, Texas, 77521

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Carrie H. Yuen · Principal Investigator

Houston Methodist Cypress Hospital

Cypress, Texas, 77429

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Site Public Contact · Contact
Carrie H. Yuen · Principal Investigator

Houston Methodist Hospital

Houston, Texas, 77030

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Site Public Contact · Contact
Carrie H. Yuen · Principal Investigator

M D Anderson Cancer Center

Houston, Texas, 77030

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Jing Christine Ye · Principal Investigator

Methodist Willowbrook Hospital

Houston, Texas, 77070

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Site Public Contact · Contact
Carrie H. Yuen · Principal Investigator

Houston Methodist West Hospital

Houston, Texas, 77094

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Site Public Contact · Contact
Carrie H. Yuen · Principal Investigator

Houston Methodist Saint John Hospital

Nassau Bay, Texas, 77058

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Carrie H. Yuen · Principal Investigator

Houston Methodist Sugar Land Hospital

Sugar Land, Texas, 77479

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Carrie H. Yuen · Principal Investigator

Houston Methodist The Woodlands Hospital

The Woodlands, Texas, 77385

Recruiting
Carrie H. Yuen · Principal Investigator

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301

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Matthew L. Ryan · Principal Investigator

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin, 54303

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Site Public Contact · Contact
Matthew L. Ryan · Principal Investigator

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601

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David E. Marinier · Principal Investigator

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, 53718

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Matthew J. Brunner · Principal Investigator

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792

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Matthew J. Brunner · Principal Investigator

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

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Anita D'Souza · Principal Investigator

Saint Vincent Hospital Cancer Center at Oconto Falls

Oconto Falls, Wisconsin, 54154

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Matthew L. Ryan · Principal Investigator

Saint Vincent Hospital Cancer Center at Sheboygan

Sheboygan, Wisconsin, 53081

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Site Public Contact · Contact
Matthew L. Ryan · Principal Investigator

Sheboygan Physicians Group

Sheboygan, Wisconsin, 53081

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Site Public Contact · Contact
Matthew L. Ryan · Principal Investigator

Saint Vincent Hospital Cancer Center at Sturgeon Bay

Sturgeon Bay, Wisconsin, 54235-1495

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Site Public Contact · Contact
Matthew L. Ryan · Principal Investigator