Effect of Prophylactic TKI Therapy Post-transplants on Ph+ ALL Undergoing Allo-HSCT With MRD Positive Pre-transplants

Phase 2

• Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; Philadelphia Chromosome Positive Acute Lymphocytic Leukemia; Tyrosine Kinase Inhibitor; Minimal Residual Disease
• Interventions: Drug: Tyrosine kinase inhibitor (TKIs)

• Registration Number: NCT03624530
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early first complete remission improves the long-term outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Relapse remains a major cause of treatment failure even after allo-HSCT. The prevention of relapse is essential for improving the outcome of Ph+ ALL. Our previous clinical trial (ID: NCT01883219) demonstrated that pre-emptive tyrosine kinase inhibitor (TKIs) administration based on minimal residual disease (MRD) and BCR-ABL mutation after allo-HSCT might reduce the incidence of relapses and improve survival for patients with Ph+ ALL. Moreover, our result suggested that Ph+ ALL with MRD positive pre-transplants had the higher rate of molecular biology relapse. In this study, we will evaluate the safety and efficacy of prophylactic TKI therapy post-transplants on Ph+ ALL undergoing allo-HSCT with MRD positive pre-transplants.

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early first complete remission improves the long-term outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Relapse remains a major cause of treatment failure even after allo-HSCT. Overall, patients experiencing relapse have a dismal prognosis despite salvage treatment with TKIs. The prevention of relapse is essential for improving the outcome of Ph+ ALL. Strategies to prevent relapse include tyrosine kinase inhibitor (TKIs) use, donor lymphocyte infusions (DLI), CAR-T and so on. At present, the utility of TKIs administration post-transplants is controversial. Our previous clinical trial (ID: NCT01883219) demonstrated that pre-emptive TKI administration based on minimal residual disease (MRD) and BCR-ABL mutation after allo-HSCT might reduce the incidence of relapses and improve survival for patients with Ph+ ALL. Moreover, we found that 58% Ph+ ALL with MRD positive pre-transplants would MRD positive post-transplants, whereas only 11.4% Ph+ ALL with MRD negative pre-transplants would MRD positive post-transplants, suggesting that Ph+ ALL with MRD positive pre-transplants had the higher rate of molecular biology relapse. In this study, we will evaluate the safety and efficacy of prophylactic TKI therapy post-transplants on Ph+ ALL undergoing allo-HSCT with MRD positive pre-transplants.

Study Timeline

• Status Verified: 2018-08
• Study Start: 2018-08
• Study First Submitted: 2018-08-02
• Study First Submitted QC: 2018-08-08
• Last Update Submitted: 2018-08-08
• Study First Posted: 2018-08-10
• Last Update Posted: 2018-08-10
• Primary Completion: 2021-07
• Study Completion: 2022-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

• Patient age of 14-65 years
• Ph+ ALL undergoing allo-HSCT with MRD positive pre-transplants
• Survival > 30 days post-transplants
• MRD negative on day +30 post-transplants

Exclusion Criteria

• Ph+ ALL undergoing allo-HSCT with MRD negative pre-transplants
• Survival <30 days post-transplants
• MRD positive on day +30 post-transplants
• Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• Patients with any conditions not suitable for the trial (investigators' decision)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylactic TKI Therapy	Tyrosine kinase inhibitor (TKIs)	Treatment with prophylactic TKI will be initiated from day +30 to +60 post-transplants. TKI was selected according to the mutation results of ABL kinase region.

Primary Outcome Measures

Name	Time	Method
Overall survival(OS)	2 year	the time from the date of transplantation to death or the last day of follow-up

Secondary Outcome Measures

Name	Time	Method
Relapse rate	2 year	the cumulative relapse rate of leukemia
Disease-free survival(DFS)	2 year	the time from the date of transplantation to relapse or death or the last day of follow-up
Adverse effects of TKI therapy	2 year	Number of participants with treatment-related adverse events and specific adverse effects including fluid retention , diarrhea, headache, nausea, rash, dyspnea, bleeding, fatigue, musculoskeletal pain, infection, vomiting, cough, abdominal pain and fever.

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China