A Study of TKI Maintenance Therapy Following Allo-HSCT in Newly Diagnosed Ph+ Adult ALL

September 29, 2021 updated by: First Affiliated Hospital Xi'an Jiaotong University

A Randomized Controlled Study of Tyrosine Kinase Inhibitor Maintenance Therapy Following Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed Philadelphia Chromesome Positive Adult Acute Lymphoblastic Leukemia

This project is a key clinical research project approved by the Clinical Research Center of the First Affiliated Hospital of Xi 'an Jiaotong University.Tyrosine kinase inhibitors (TKI) combined with chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) are routinely used in patients with philadelpha-positive lymphoblastic leukemia (Ph+ALL). However, TKI maintenance therapy post-HSCT remains controversial. In this study, Ph+ALL patients are enrolled and given dasatinib combined with chemotherapy followed by allo-HSCT. Then patients in the group A continuing to use dasatinib for 1 year is compared with those in the group B receiving dasatinib for 6 months after HSCT. The measurable residual disease (MRD), complete remission (CR), overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and the incidence of graft versus host disease (GVHD) will be observed to determine the optimal duration of TKI maintenance therapy post-HSCT.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

About 25% of adult patients with acute lymphoblastic leukemia (ALL) are associated with t (9; 22), positive philadelphia chromosome (Ph+ ALL), in whom BCR/ABL fusion gene can be detected in the bone marrow and peripheral blood. Although current treatment strategies using tyrosine kinase inhibitors (TKIs) such as dasatinib combined with chemotherapy have achieved high complete remission (CR) rates, the duration of remission is short, and most Ph+ ALL patients relapse within 2 years. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) bridging to CR remains the only strategy to cure Ph+ ALL. However, TKI maintenance therapy post-HSCT remains controversial. In this study, Ph+ALL patients are enrolled. The participants will receive dasatinib combined with induction and consolidation chemotherapy to obtain molecular remission and then undergo allo-HSCT. After the above treatments, the patients will be randomly divided into two groups. The subjects in the group A will continue to use dasatinib for 1 year, while the patients in the group B receive dasatinib for 6 months post-HSCT. The measurable residual disease (MRD), CR, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and the incidence of graft versus host disease (GVHD) will be observed to determine the optimal duration of TKI maintenance therapy post-HSCT.

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Pengcheng He
  • Phone Number: 0086-18991232609
  • Email: hepc@163.com

Study Contact Backup

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • Recruiting
        • First Affiliated Hospital of Xian Jiaotong University
        • Contact:
          • Pengcheng He
          • Phone Number: 0086-18991232609
          • Email: hepc@163.com
        • Contact:
        • Principal Investigator:
          • Xiaoning Wang
        • Principal Investigator:
          • Huachao Zhu
        • Principal Investigator:
          • Juan Ren
        • Principal Investigator:
          • Ying Chen
        • Principal Investigator:
          • Ting Fan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18-65 years old, newly diagnosed as Ph+ALL.
  • Sign the informed consent.
  • Have appropriate allo-HSCT donors.
  • Accept allo-HSCT.
  • Accept follow-up.

Exclusion Criteria:

  • Liver and kidney function impairment: serum transaminase > 2 times of the upper limit of normal value, total bilirubin > 1.5 times of the upper limit of normal value, serum inosine > the upper limit of normal value (97 umol/L).
  • Active hepatitis B, hepatitis C or tuberculosis infection.
  • Can not tolerate the adverse effects of dasatinib.
  • Pregnancy.
  • Diagnosis of mental disorders.
  • Failed to reach molecular complete remission (MCR) after the early treatment.
  • Do not accept follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dasatinib for 1 year
After the allo-HSCT treatment, the patients in this group will continue to take dasatinib orally for 1 year.
Drug: Dasatinib
Take Dasatinib orally for 1 year or 6 months post-HSCT.
Other Names:
  • Dasatinib tablet
Experimental: Dasatinib for 6 months
After the allo-HSCT treatment, the patients in this group will receive dasatinib for 6 months.
Drug: Dasatinib
Take Dasatinib orally for 1 year or 6 months post-HSCT.
Other Names:
  • Dasatinib tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients with Measurable Residual Disease (MRD) Positivity
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
MRD means the subclinical levels of residual leukemia.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Percentage of Patients with Complete Remission (CR)
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
CR means that the blood counts have returned to normal, the leukemia cannot be seen when a bone marrow sample is examined under the microscope, and the signs and symptoms of the ALL are gone.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free Survival (DFS), months
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
The measure of time after allo-HSCT during which no sign of ALL is found.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Overall Survival (OS), months
Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.
The length of time from the date of allo-HSCT that Ph+ ALL patients are still alive.
From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.
Non-relapse Mortality (NRM), rate or percentage
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
NRM means death without recurrent or progressive disease after allo-HSCT.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Incidence of graft versus host disease (GVHD), rate or percentage
Time Frame: From date of randomization until the date of GVHD occurrence or date of death from any cause, whichever came first, assessed up to 36 months.
GVHD is a condition that might occur after allo-HSCT. In GVHD, the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body.
From date of randomization until the date of GVHD occurrence or date of death from any cause, whichever came first, assessed up to 36 months.
Adverse Effects (AE)
Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.
An adverse effect is any untoward medical occurrence in clinical investigation subject administered dasatinib and which does not necessarily have a causal relationship with this treatment.
From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital Xi'an Jiaotong University

Investigators

  • Study Chair: Pengcheng He, First Affiliated Hospital of Xian Jiaotong University
  • Study Director: Xiaoning Wang, First Affiliated Hospital of Xian Jiaotong University
  • Principal Investigator: Huachao Zhu, First Affiliated Hospital of Xian Jiaotong University
  • Principal Investigator: Juan Ren, First Affiliated Hospital of Xian Jiaotong University
  • Principal Investigator: Ying Chen, First Affiliated Hospital of Xian Jiaotong University
  • Principal Investigator: Ting Fan, First Affiliated Hospital of Xian Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 6, 2021

Primary Completion (Anticipated)

June 30, 2023

Study Completion (Anticipated)

June 30, 2023

Study Registration Dates

First Submitted

August 17, 2021

First Submitted That Met QC Criteria

August 26, 2021

First Posted (Actual)

August 27, 2021

Study Record Updates

Last Update Posted (Actual)

October 1, 2021

Last Update Submitted That Met QC Criteria

September 29, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XJTU1AF-CRF-2020-002-1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Precursor Cell Lymphoblastic Leukemia-Lymphoma

Clinical Trials on Dasatinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guatemala

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe