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

Nanfang Hospital, Southern Medical University

Status and phase: Unknown; Phase 3; Phase 2

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

Treatments: Drug: Tyrosine kinase inhibitor (TKIs)

Study type: Interventional

Funder types: Other

Identifiers

NCT03624530

TKI post-HSCT- MRD+Ph+ALL-2018

Details and patient eligibility

About

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.

Full 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.

Enrollment: 82 estimated patients

Sex: All

Ages: 14 to 65 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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82 participants in 2 patient groups

Prophylactic TKI Therapy

Experimental group

Description:

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.

Treatment:

Drug: Tyrosine kinase inhibitor (TKIs)

No TKI therapy

No Intervention group

Description:

Prophylactic TKI will not be given.