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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Prophylactic Tyrosine Kinase Inhibitor Therapy Post-transplants on Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia Undergoing Allo-HSCT With Minimal Residual Disease Positive Pre-transplants

Conditions
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Philadelphia Chromosome Positive Acute Lymphocytic Leukemia, Tyrosine Kinase Inhibitor, Minimal Residual Disease, Allogeneic Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Tyrosine kinase inhibitor (TKIs)


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylactic TKI Therapy<br>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. | Drug: Tyrosine kinase inhibitor (TKIs)<br>* TKI was selected according to the mutation results of ABL kinase region. Imatinib was initiated at a dose of 200mg/d, dasatinib at a dose of 50mg/d, and ponatinib at a dose of 30mg/d. Then increase the dosage of TKI gradually and increase to therapeutic dose within one month. The duration of TKI was 180 days.<br>|
| No Intervention: No TKI therapy<br>Prophylactic TKI will not be given. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival(OS) | the time from the date of transplantation to death or the last day of follow-up | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse rate | the cumulative relapse rate of leukemia | 2 year | 
| Disease-free survival(DFS) | the time from the date of transplantation to relapse or death or the last day of follow-up | 2 year | 
| Adverse effects of TKI therapy | 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. | 2 year |