Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1/Phase 2

Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

NCT ID: NCT03104491Sponsor: Leland MethenyLast updated: 2025-06-05

Summary

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects. The Phase II portion of this study is to see what side effects are seen with medication after transplant. Inotuzumab ozogamicin is a combination of an antibody and chemotherapy which has been shown to have significant activity against relapsed/refractory acute lymphocytic leukemia (ALL). Inotuzumab ozogamicin is considered experimental in this study.

Detailed description

Study Design This is a Phase I/II study of inotuzumab ozogamicin for the treatment of patients who underwent allogeneic transplantation for ALL and have a high risk of relapse. The Phase I portion of this study will be a 3+3 dose escalation trial. This is followed by a phase 2 cohort at the recommended Phase 2 dose (RP2D). Participants will receive study treatment up to 4 cycles until relapse of disease, unacceptable toxicity, or death, whichever occurs first Phase I: Inotuzumab Ozogamicin Dosing Escalation Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. Phase II: Inotuzumab Ozogamicin Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. In order to be included in the safety profile endpoint review, subjects must have received at least of 1 cycle of treatment. Primary Objective Phase I: To define a post hematopoietic stem cell transplantation maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of inotuzumab ozogamicin. Phase II: To assess the efficacy of inotuzumab ozogamicin as measured by diseasefree survival (DFS) at one year. Secondary Objective(s) Phase I: * To evaluate disease-free survival (DFS), nonrelapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year. * To determine safety profile of inotuzumab ozogamicin after transplant including the incidence of myeloid toxicity and secondary graft failure and the rate of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). * To determine if inotuzumab ozogamicin at these doses is effective at eradicating minimal residual disease in this cohort of participants Phase II: * To assess additional evidence of efficacy and safety as measured by non-relapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year. * To determine if inotuzumab ozogamicin at these doses is effective at eradicating MRD. * To confirm the safety profile of inotuzumab ozogamicin therapy after transplant including myeloid toxicity, secondary graft failure, and the rate of VOD/SOS. * To evaluate the pharmacokinetics of inotuzumab ozogamicin post allogeneic transplant

Arms & interventions

  • DrugInotuzumab Ozogamicin

    Inotuzumab ozogamicin, IV, 28 day cycles Phase 1 dosages: Dose Level -2 (0.1 mg/m\^2) Dose Level -1 (0.2 mg/m\^2) Dose Level 0 (0.3 mg/m\^2) Dose Level 1 (0.4 mg/m\^2) Dose Level 2 (0.5 mg/m\^2) Dose Level 3 (0.6 mg/m\^2)

Outcome measures

Primary

  • Phase I MTD

    Defined post hematopoietic stem cell transplantation MTD

    Time frame: Up to 112 days (16 weeks)

  • Phase I DLTs

    Frequency of DLTs during the first two cycles in ALL-participants

    Time frame: Up to 112 days (16 weeks)

  • Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Time frame: At 3 months after initial treatment

  • Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Time frame: At 6 months after initial treatment

  • Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Time frame: At 9 months after initial treatment

  • Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Time frame: At 1 year after initial treatment

  • Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Time frame: Post first dose of inotuzumab ozogamicin

Secondary

  • Phase I Median DFS

    Time frame: At 3 months after initial treatment

  • Phase I Median DFS

    Time frame: At 6 months after initial treatment

  • Phase I Median DFS

    Time frame: At 9 months after initial treatment

  • Phase I Median DFS

    Time frame: At 1 year after initial treatment

  • Phase I Median DFS

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase I NRM

    Time frame: At 3 months after initial treatment

  • Phase I NRM

    Time frame: At 6 months after initial treatment

  • Phase I NRM

    Time frame: At 9 months after initial treatment

  • Phase I NRM

    Time frame: At 1 year after initial treatment

  • Phase I NRM

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase I Relapse

    Time frame: At 3 months after initial treatment

  • Phase I Relapse

    Time frame: At 6 months after initial treatment

  • Phase I Relapse

    Time frame: At 9 months after initial treatment

  • Phase I Relapse

    Time frame: At 1 year after initial treatment

  • Phase I Relapse

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase I Relapse-related mortality

    Time frame: At 3 months after initial treatment

  • Phase I Relapse-related mortality

    Time frame: At 6 months after initial treatment

  • Phase I Relapse-related mortality

    Time frame: At 9 months after initial treatment

  • Phase I Relapse-related mortality

    Time frame: At 1 year after initial treatment

  • Phase I Relapse-related mortality

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase I Median OS

    Time frame: At 3 months after initial treatment

  • Phase I Median OS

    Time frame: At 6 months after initial treatment

  • Phase I Median OS

    Time frame: At 9 months after initial treatment

  • Phase I Median OS

    Time frame: At 1 year after initial treatment

  • Phase I Median OS

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase I Incidence of myeloid toxicity

    Time frame: At 1 year

  • Phase I Incidence of secondary graft failure

    Time frame: At 1 year

  • Phase I incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS)

    Time frame: At 1 year

  • Phase I rate of VOD/SOS - number of participants affected

    Time frame: At 1 year

  • Phase I - Percent of participants with grade 3 + AE/SAEs

    Time frame: At 1 year

  • Phase II Non-relapse mortality (NRM)

    Time frame: At 3 months after initial treatment

  • Phase II Relapse

    Time frame: At 6 months after initial treatment

  • Phase II Relapse

    Time frame: At 9 months after initial treatment

  • Phase II Relapse-related mortality

    Time frame: At 1 year after initial treatment

  • Phase II Relapse-related mortality

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase II Median OS

    Time frame: At 3 months after initial treatment

  • Phase II Median OS

    Time frame: At 6 months after initial treatment

  • Phase II Median OS

    Time frame: At 9 months after initial treatment

  • Phase II Median OS

    Time frame: At 1 year after initial treatment

  • Phase II Median OS

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase II Response Rate

    Time frame: At 3 months after initial treatment

  • Phase II Response Rate

    Time frame: At 6 months after initial treatment

  • Phase II Response Rate

    Time frame: At 9 months after initial treatment

  • Phase II Response Rate

    Time frame: At 1 year after initial treatment

  • Phase II Response Rate

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  • Phase II Incidence of myeloid toxicity

    Time frame: At 1 year

  • Phase II Incidence of secondary graft failure

    Time frame: At 1 year after initial treatment

  • Phase I incidence of VOD/SOS

    Time frame: At 1 year

  • Phase II rate of VOD/SOS - number of participants affected

    Time frame: At 1 year

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 1 (C1D1) after 1 hour (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 1 (C1D1) after 4 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 7 (C1D7) (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle1 Day 1 (C1D1) after 1 hour (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle1 Day 1 (C1D1) after 4 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 1 Day 7 (C1D7) (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days)

  • Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days)

Eligibility criteria

Sex: AllAge: 16 Years to 75 YearsHealthy volunteers: No
Inclusion Criteria: Phase 1 Inclusion Criteria * Diagnosis of CD22-positive Acute Lymphoblastic Leukemia * Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia * Patients who are between T+40 and T+100 after allogeneic transplantation. Patients must receive their first dose of inotuzumab at or before T+100. * Patients who have/are either: * Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation ---Pre- or Post-Transplant Minimal Residual Disease defined by: ----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication. * In second or third complete remission at the time of allogeneic transplantation * Treated with reduced intensity regimens or non-myeloablative conditioning regimens * Lymphoid blast crisis of CML * Are relapsed or refractory to at least 1 line of chemotherapy * Philadelphia-like ALL * Patients who have evidence of donor chimerism after allogeneic transplantation. * ECOG Performance status \< 2 * Participants must have ANC \> 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count \> 50,000/µL for 7 days. * Able to adhere to the study visit schedule and other protocol requirements. * Participants must have the ability to understand and the willingness to sign a written informed consent document. Phase 2 Inclusion Criteria * Diagnosis of CD22-positive Acute Lymphoblastic Leukemia * Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia * Patients who are between T+40 and T+100 after allogeneic transplantation * Patients who have/are either: * Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation ---Post-Transplant Minimal Residual Disease defined by: ----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication. * In second or third complete remission at the time of allogeneic transplantation * Treated with reduced intensity regimens as defined per institutional standard of practice * Lymphoid blast crisis of CML * Are relapsed or refractory to at least 1 line of chemotherapy * Philadelphia-like ALL * Patients who have \> 80% donor chimerism after allogeneic transplantation. * Philadelphia chromosome positive ALL must have failed at least 1 TKI * ECOG Performance status \< 1 * pre-transplant evaluation, see 10.1.1 * Participants must have ANC \> 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count \> 50,000/µL for 7 days. * Able to adhere to the study visit schedule and other protocol requirements. * Participants must have the ability to understand and the willingness to sign a written informed consent document. Phase 1 and 2 Exclusion Criteria: * Patients with clinical evidence of disease progression prior to enrollment * Persistent prior treatment toxicities Grade 2 and above according to NCI CTCAE Version 4.03 (with the exception for alopecia, neuropathy, etc.) * Patients with inadequate organ function as defined by: * Creatinine clearance \< 30ml/min * Bilirubin \> 2X institutional upper limit of normal * AST (SGOT) \> 2X institutional upper limit of normal * ALT (SGPT) \> 2X institutional upper limit of normal * GVHD grade III or IV (for patients with a prior allogeneic transplant). * Active acute or chronic GVHD of the liver (for patients with a prior allogeneic transplant) * History of VOD * Use of concomitant TKI or sirolimus * Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) * Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant or breastfeeding women are excluded from this study because inotuzumab ozogamicin may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with inotuzumab ozogamicin, breastfeeding should be discontinued if the mother is treated with inotuzumab ozogamicin. These potential risks may also apply to other agents used in this study. * Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) * Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) * Participation in any other investigational drug study or had exposure to any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater) * Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. * Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds

Study locations (7)

The University of Kansas Cancer Center

Westwood, Kansas, 66205

Recruiting
Nausheen Ahmed, MD · Contact

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting
Roman Shapiro, MD · Contact

University of Nebraska Medical Center

Omaha, Nebraska, 68106

Recruiting
Vijaya Bhatt, MD · Contact

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Active Not Recruiting

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065

Recruiting
Leland Metheny, MD · Contact
Leland Metheny · Principal Investigator

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195

Active Not Recruiting

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210

Recruiting
Sumithira Vasu, MBBS · Contact

References

  • Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.(PubMed)
  • Metheny LL, Sobecks R, Cho C, Fu P, Margevicius S, Wang J, Ciarrone L, Kopp S, Convents RD, Majhail N, Caimi PF, Otegbeye F, Cooper BW, Gallogly M, Malek E, Tomlinson B, Gerds AT, Hamilton B, Giralt S, Perales MA, de Lima M. A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia. Blood Adv. 2024 Mar 26;8(6):1384-1391. doi: 10.1182/bloodadvances.2023011514.(PubMed)