Philadelphia Chromosome Positive Acute Lymphocytic Leukemia, Tyrosine Kinase Inhibitor, Minimal Residual Disease, Allogeneic Hematopoietic Stem Cell Transplantation
Conditions
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.
Interventions
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.
Sponsors
Peking University People's Hospital
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Guangzhou First People's Hospital
Zhujiang Hospital
Third Affiliated Hospital, Sun Yat-Sen University
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival(OS) | 2 year | the time from the date of transplantation to death or the last day of follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactLi Xuan
Outcome results
None listed