Acute Lymphoid Leukemia
Conditions
Brief summary
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.
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)
Interventions
DRUGInotuzumab ozogamicin
1. st dose is given after D+60：inotuzumab 0.3mg/m2 2. nd dose is given after 1 month：inotuzumab 0.6mg/m2
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DFS | at one year after HSCT | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse | at one year after HSCT | Defined as time from date of HSCT to the date of first relapse. Reported as Cumulative Incidence |
| NRM | at one year after HSCT | Defined as time from date of first dose to death due to any cause without prior relapse. |
| Overall survival | at one year after HSCT | 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 |
| Incidence of secondary graft failure(GF) | at one year after HSCT | 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 |
| Percent of participants with AE/SAEs | at one year after HSCT | safety profile of intervention as measured by percent of participants with any grade AE/SAEs |
| Incidence of hematological toxicity | at one year after HSCT | Number of patients who develop hematological toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia, etc. |
Countries
China
Outcome results
None listed