Clinical trial NCT03624530: Effect of Prophylactic TKI Therapy Post-transplants on Ph+ ALL Undergoing Allo-HSCT With MRD Positive Pre-transplants
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Philadelphia Chromosome Positive Acute Lymphocytic Leukemia
Tyrosine Kinase Inhibitor
Minimal Residual Disease
Allogeneic Hematopoietic Stem Cell Transplantation
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Guangzhou First People's Hospital
name: Zhujiang Hospital
name: Third Affiliated Hospital, Sun Yat-Sen University
First posted: 2018-08-10
Enrollment: 82
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall survival(OS)
timeFrame: 2 year
Secondary outcomes:
measure: Relapse rate
timeFrame: 2 year
measure: Disease-free survival(DFS)
timeFrame: 2 year
measure: Adverse effects of TKI therapy
timeFrame: 2 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Qifa Liu
role: PRINCIPAL_INVESTIGATOR
References: