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

Primary Purpose

Philadelphia Chromosome Positive Acute Lymphocytic Leukemia, Tyrosine Kinase Inhibitor, Minimal Residual Disease

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tyrosine kinase inhibitor (TKIs)
Sponsored by
Nanfang Hospital, Southern Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Philadelphia Chromosome Positive Acute Lymphocytic Leukemia

Eligibility Criteria

14 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Department of Hematology,Nanfang Hospital, Southern Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Prophylactic TKI Therapy

No TKI therapy

Arm 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.

Prophylactic TKI will not be given.

Outcomes

Primary Outcome Measures

Overall survival(OS)
the time from the date of transplantation to death or the last day of follow-up

Secondary Outcome Measures

Relapse rate
the cumulative relapse rate of leukemia
Disease-free survival(DFS)
the time from the date of transplantation to relapse or death or the last day of follow-up
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.

Full Information

First Posted
August 2, 2018
Last Updated
August 8, 2018
Sponsor
Nanfang Hospital, Southern Medical University
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT03624530
Brief Title
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2018 (Anticipated)
Primary Completion Date
July 2021 (Anticipated)
Study Completion Date
July 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nanfang Hospital, Southern Medical University
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Philadelphia Chromosome Positive Acute Lymphocytic Leukemia, Tyrosine Kinase Inhibitor, Minimal Residual Disease, Allogeneic Hematopoietic Stem Cell Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Prophylactic TKI Therapy
Arm Type
Experimental
Arm 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.
Arm Title
No TKI therapy
Arm Type
No Intervention
Arm Description
Prophylactic TKI will not be given.
Intervention Type
Drug
Intervention Name(s)
Tyrosine kinase inhibitor (TKIs)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival(OS)
Description
the time from the date of transplantation to death or the last day of follow-up
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Relapse rate
Description
the cumulative relapse rate of leukemia
Time Frame
2 year
Title
Disease-free survival(DFS)
Description
the time from the date of transplantation to relapse or death or the last day of follow-up
Time Frame
2 year
Title
Adverse effects of TKI therapy
Description
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.
Time Frame
2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Li Xuan
Phone
+86-020-62787883
Email
356135708@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qifa Liu
Organizational Affiliation
Nanfang Hospital, Southern Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematology,Nanfang Hospital, Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Xuan
Phone
+86-020-62787883
Email
356135708@qq.com
First Name & Middle Initial & Last Name & Degree
Qifa Liu

12. IPD Sharing Statement

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

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