Phase II Study of Post-Transplant Low-Dose Inotuzumab Ozogamicin to Prevent Relapse of Acute Lymphoblastic Leukemia

Phase II Study Assessing the Efficacy and Safety of Post-Transplant Low-Dose Inotuzumab Ozogamicin to Prevent Relapse of High Risk Acute Lymphoblastic Leukemia

To learn about the safety of post-HSCT two dose Inotuzumab Ozogamicin to participants with high risk B cell acute lymphoblastic leukemia(B-ALL). Also, to learn if giving Inotuzumab Ozogamicin to post-HSCT patients with high-risk B- ALL can help to reduce relapse and prolong disease free survival and overall survival.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoid Leukemia
• Intervention / Treatment: Drug: Inotuzumab ozogamicin

Detailed Description

This is a Phase II study of inotuzumab ozogamicin for the treatment of patients who underwent transplantation for ALL and have a high risk of relapse. Participants will receive study treatment two doses until relapse of disease, unacceptable toxicity, or death, whichever occurs first Primary Objective

• To assess the efficacy of inotuzumab ozogamicin as measured by disease free survival (DFS) at one year.

Secondary Objective(s)

• To evaluate relapse rate, 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 hematological toxicity, secondary graft failure and other adverse event(AE)/severe adverse event(SAEs)

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
    • Contact: Erlie Jiang; Phone Number: +86-15122538106; Email: jiangerlie@ihcmas.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
• Patients who underwent an allogeneic hematopoietic stem cell transplantation(HSCT) from any donor source or auto-HSCT for acute lymphocytic leukemia
• Patients who are after T+60 after transplantation

• Patients who have/are either:

  • High risk B-ALL: (1) high white blood cell(WBC) count when newly diagnosed, (2) Poor risk group according to NCCN guideline 2021 of Acute Lymphoblastic
  • Leukemia
  • Relapsed or refractory to at least 1 line of treatment
  • Minimal residual disease(MRD) positive before HSCT, including flow cytometry and cytogenetic test
• Patients who have > 99% donor chimerism after allogeneic transplantation.
• Eastern Cooperative Oncology Group(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.
• ≥ 18 years old, including male and female
• Participants must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients with 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 and can't tolerate the study treatment determined by investigator as defined by:

  • Severe renal deficiency, with creatinine clearance < 50ml/min
  • Severe hepatic deficiency
  • Bilirubin, aspartate aminotransferase(AST), and/or ALT(ALT) > 2X institutional upper limit of normal
  • Severe cardiac or pulmonary deficiency
• Graft-versus-host disease(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 veno-occlusive disease(VOD)
• 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.
• 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.)
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inotuzumab ozogamicin	Drug: Inotuzumab ozogamicin; st dose is given after D+60：inotuzumab 0.3mg/m2; nd dose is given after 1 month：inotuzumab 0.6mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	Efficacy as measured by 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 HSCT 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)".	at one year after HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined from time from HSCT to death due to any cause Defined from time from date of HSCT to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10	at one year after HSCT
Relapse	Defined as time from date of HSCT to the date of first relapse. Reported as Cumulative Incidence	at one year after HSCT
NRM	Defined as time from date of first dose to death due to any cause without prior relapse.	at one year after HSCT
Incidence of hematological toxicity	Number of patients who develop hematological toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia, etc.	at one year after HSCT
Incidence of secondary graft failure(GF)	Number of patients who develop secondary graft failure while on study, defined as: Either cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced	at one year after HSCT
Percent of participants with AE/SAEs	safety profile of intervention as measured by percent of participants with any grade AE/SAEs	at one year after HSCT

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: May 21, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 28, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immunoconjugates; Immunotoxins; Inotuzumab Ozogamicin
• Other Study ID Numbers: IIT2024022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No