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RecruitingInterventionalPhase 2

Immunoglobulin Replacement Therapy and Infectious Complications After CD19-Targeted CAR-T-Cell Therapy

NCT ID: NCT05952804Sponsor: Fred Hutchinson Cancer CenterLast updated: 2026-04-21

Summary

This phase II trial compares the effects of immunoglobulin replacement therapy with a placebo for preventing infectious complications in patients receiving CD19 chimeric antigen receptor (CAR)-T cell therapy. Hypogammaglobulinemia is a common complication in patients who receive CD19 CAR-T cell therapy. This is a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is high. Immunoglobulin replacement therapy works by replacing the body's immunoglobulin G (IgG) antibodies with donor blood product derived IgG antibodies that may help prevent infection. IgG antibodies are often depleted as a result of CAR-T therapy. Giving immunoglobulin replacement therapy may prevent infectious complications in patients receiving CD19 CAR-T cell therapy.

Detailed description

OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive immunoglobulin replacement therapy (IGRT) with intravenous immune globulin (IVIG) within 14 days prior to CD19 CAR-T-cell infusion. Patients then undergo CD19 CAR-T therapy. Patients receive IVIG monthly, starting 28 days after CD19 CAR-T therapy for up to 4 months in the absence of unacceptable toxicity, relapse of the underlying disease, or subsequent hematopoietic cell transplant. Patients also undergo blood sample collection throughout the study. ARM II: Patients receive placebo with normal saline IV within 14 days prior to CD19 CAR-T treatment. Patients then undergo CD19 CAR-T-cell infusion. Patients receive normal saline monthly, starting 28 days after CD19 CAR-T therapy for up to 4 months in the absence of unacceptable toxicity, relapse of the underlying disease, or subsequent hematopoietic cell transplant. Patients also undergo blood sample collection throughout the study. After completion of study treatment, patients are followed up monthly through up to 6 months after CD19 CAR-T-cell infusion.

Arms & interventions

  • BiologicalImmune Globulin Infusion (Human), 10% Solution

    Given IV

  • BiologicalAnti-CD19 CAR T Cells Preparation

    Given CAR-T treatment

  • OtherSaline

    Given IV

  • ProcedureBiospecimen Collection

    Undergo blood sample collection

  • OtherSurvey Administration

    Ancillary studies

  • OtherElectronic Health Record Review

    Ancillary studies

Outcome measures

Primary

  • Incidence rate of serious bacterial infections in the modified intention-to-treat (mITT) population

    Grade 2 or 3 bacterial infections. Only microbiologically confirmed infections will be included. Microbiological documentation of an infection consists of isolation of the pathogen by culture from a sterile (definite) or nonsterile (probable) site (if from a nonsterile site, the organism had to be clinically judged to be pathogenic). Will describe the number and type of infections in each study arm and calculate incidence rate estimates and 95% confidence intervals (CIs) for infections. Will compare serious bacterial infection incidence rates between study arms using negative binomial regression with an offset to account for days-at-risk. Will construct multivariable Cox proportional hazards models of time-to-first serious bacterial infection.

    Time frame: From randomization through day 168 post chimeric antigen receptor (CAR) T-cell treatment (CARTx)

Secondary

  • Incidence rate of serious bacterial infections in ITT and per-protocol populations and of any serious infection or any infection after CD19 CARTx

    Time frame: From randomization through day 168 post CARTx

  • Levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG

    Time frame: From randomization through day 168 post CARTx

  • Health resource utilization (HRU)

    Time frame: Up to 6 months post CARTx

  • Incidence and severity of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS)

    Time frame: Up to 6 months post CARTx

  • CAR T-cell expansion: Peak Plasma Concentration (Cmax)

    Time frame: Up to 6 months post CARTx

  • CAR T-cell expansion: area under the curve (AUC)

    Time frame: Up to 6 months post CARTx

  • CAR T-cell persistence

    Time frame: Up to 6 months post CARTx

  • CAR T-cell phenotype and function

    Time frame: At day 14 post CARTx

  • Immune cell subset phenotypes and functional makers

    Time frame: At 6 months post CARTx

  • IgA and IgM levels

    Time frame: At 6 months post CARTx

  • Health related quality of life (HRQOL)

    Time frame: From baseline up to 6 months post CARTx

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent * For patients with medical incapacity or impaired consciousness such that they are not able to give fully informed voluntary consent, the subjects' legal representative must sign an institutional review board (IRB) approved informed consent document prior to the initiation of any screening or study-specific procedures * Participants must be 18 years of age or older * Participants will receive an Food and Drug Administration (FDA)-approved CD19-CAR T-cell product for the treatment of hematologic malignancies. Patients receiving an FDA-approved product are eligible even if the product is being administered as part of a clinical trial or expanded access program (e.g., product is 'out of specification'; concomitant anti-tumor treatment such as acalabrutinib) * Serum total IgG \< 600mg/dL within the prior three months * SUBSEQUENT INFUSIONS: Received an FDA-approved CD19-CAR T-cell product for the treatment of hematologic malignancies Exclusion Criteria: * Primary congenital selective IgA deficiency * Prior serious adverse event/s related to intravenous immune globulin (IVIG) administration * Known serious allergy to any component of IVIG * Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study or interfere with the patient's ability to participate for the full duration of the study or would put the patient at undue risk as judged by the investigator, such that it is not in the best interest of the patient to participate in this study * SUBSEQUENT INFUSIONS: Ongoing symptoms of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) meeting criteria for grade 3 or higher * SUBSEQUENT INFUSIONS: Primary congenital selective IgA deficiency * SUBSEQUENT INFUSIONS: Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study or interfere with the patient's ability to participate for the full duration of the study or would put the patient at undue risk as judged by the Investigator, such that it is not in the best interest of the patient to participate in this study * SUBSEQUENT INFUSIONS: Receipt of additional therapy for persistence or relapse of the patient's primary malignancy * SUBSEQUENT INFUSIONS: Receipt of bone marrow transplant (allogeneic or autologous) * SUBSEQUENT INFUSIONS: Any serious adverse event (SAE), clinically significant adverse event (AE), severe laboratory abnormality, intercurrent illness, or other medical condition that indicates to the Investigator that continued participation is not in the best interest of the participant

Study locations (7)

City of Hope Cancer Center

Duarte, California, 91010

Recruiting
Sanjeet Dadwal, MD · Principal Investigator

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136

Recruiting
Jay Spiegel, MD · Principal Investigator

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting
Frederick Locke, MD · Principal Investigator

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114

Recruiting
Matthew Frigault, MD · Principal Investigator

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
Miguel-Angel Perales, MD · Principal Investigator

Oregon Health and Science University (OHSU) Knight Cancer Institute

Portland, Oregon, 97239

Recruiting
Amrita Desai, MD, MPH · Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

Recruiting
Joshua Hill, MD · Contact
Joshua Hill, MD · Principal Investigator