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

Minimal Residual Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03624530
• Other study ID #: TKI post-HSCT- MRD+Ph+ALL-2018
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 2018
• Est. completion date: July 2022

Study information

• Verified date: August 2018
• Source: Nanfang Hospital of Southern Medical University
• Contact: Li Xuan
• Phone: +86-020-62787883
• Email: 356135708[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 82
• Est. completion date: July 2022
• Est. primary completion date: July 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Allogeneic Hematopoietic Stem Cell Transplantation
• Leukemia
• Leukemia, Lymphoid
• Minimal Residual Disease
• Neoplasm, Residual
• Philadelphia Chromosome
• Philadelphia Chromosome Positive Acute Lymphocytic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Tyrosine Kinase Inhibitor

Intervention

Drug:
• Tyrosine kinase inhibitor (TKIs)
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.

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (6)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	Guangzhou First People's Hospital, Peking University People's Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Third Affiliated Hospital, Sun Yat-Sen University, Zhujiang Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival(OS)	the time from the date of transplantation to death or the last day of follow-up	2 year
Secondary	Relapse rate	the cumulative relapse rate of leukemia	2 year
Secondary	Disease-free survival(DFS)	the time from the date of transplantation to relapse or death or the last day of follow-up	2 year
Secondary	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