Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

NCT ID: NCT03104491

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-31
• Study Completion Date: 2027-05-31

Brief 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

Conditions

Acute Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Inotuzumab Ozogamicin

Phase I:

A maximum of 4 cycles will be allowed and doses will be adjusted in 0.1mg/m2 increments using a dose escalation scale depending on tolerability. Total range of dose levels for participants is 0.1-0.6mg/m^2.

Phase II:

Participants will be enrolled until all Phase I participants have been followed and assessed for toxicity for at least 4 weeks after the fourth treatment dose of inotuzumab ozogamicin or 4 weeks after the participant goes off treatment, whichever comes first. Doses to be administered will be determined in the phase I portion of the study. The recommended phase 2 dose is 0.3mg/m2. Repeat cycles every 28 days for up to 4 cycles

Group Type: EXPERIMENTAL

Inotuzumab Ozogamicin

Intervention Type: DRUG

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)

Interventions

Inotuzumab 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)

Intervention Type: DRUG

Eligibility Criteria

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.

• 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.

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leland Metheny

OTHER

Sponsor Role: lead

Responsible Party

Leland Metheny

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Leland Metheny, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Locations

The University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status: RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status: RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status: ACTIVE_NOT_RECRUITING

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status: RECRUITING

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status: ACTIVE_NOT_RECRUITING

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Leland Metheny, MD

Role: CONTACT

CTUReferral@UHhospitals.org

1-800-641-2422

Ron Sobecks, MD

Role: CONTACT

sobeckr@ccf.org

216-444-6833

Facility Contacts

Nausheen Ahmed, MD

Role: primary

nahmed5@kumc.edu

Roman Shapiro, MD

Role: primary

Roman_Shapiro@DFCI.HARVARD.EDU

Vijaya Bhatt, MD

Role: primary

Vijaya.bhatt@unmc.edu

Leland Metheny, MD

Role: primary

CTUReferral@UHhospitals.org

800-641-2422

Sumithira Vasu, MBBS

Role: primary

Sumithira.Vasu@osumc.edu

References

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.

Reference Type: DERIVED

PMID: 38170741 (View on PubMed)

Other Identifiers

CASE1916

Identifier Type: -

Identifier Source: org_study_id