Dasatinib Combined With Chemotherapy in Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

August 2, 2022 updated by: wang, jianxiang, Institute of Hematology & Blood Diseases Hospital

Dasatinib Plus Multi-agent Chemotherapy for New Diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

In this single-center, open-label, no control,prospective clinical trial, a total of 30 Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients will be enrolled. Dasatinib 100 mg per day will be given orally along with combination chemotherapy starting day 8 of induction chemotherapy. Dasatinib will be given continuously (if it's tolerable) for 2 years since achievement of complete remission (CR) as part of consolidation chemotherapy and maintenance therapy.Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. The purpose of current study is to determine the clinical efficacy and tolerability of combination therapy of Dasatinib with multi-agent chemotherapy in newly-diagnosed Ph+ ALL.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In this single-center, open-label, Phase II study, nonrandomized,no control,prospective clinical trial,a total of 30 Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients will be enrolled.Patients will be diagnosed according to morphologic,immunologic, cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype, cytogenetic and molecular genetic (BCR/ABL gene, qualitative and quantitative analysis) examination.

Dasatinib 100 mg per day will be given orally along with combination chemotherapy starting day 8 of induction chemotherapy. Dasatinib will be given continuously (if it's tolerable) for 2 years since achievement of complete remission (CR) as part of consolidation chemotherapy and maintenance therapy.Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT),or patients who keep BCR/ABL negative can receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. Total duration of follow-up will be 2 year after last enrollment.

Pre-treatment evaluation will include complete blood count (CBC) with reticulocyte count, chemistry, electrolytes, coagulation, hepatitis profile, chest X-ray.Evaluation during treatment will include: CBC every two days during myelosuppression, chemistry, electrolytes, coagulation before each cycles of chemotherapy. Quantitative PCR (RQ-PCR) for Bcr-Abl will be done from bone marrow mononuclear cells at diagnosis, at CR, and before each cycles of consolidation chemotherapy,then every 3 months during maintenance therapy. For patients who undergo allogeneic HSCT, quantitative PCR for Bcr-Abl will be done from bone marrow mononuclear cells at the initiation of conditioning, and then every 3 months. PCR will be done in IS standardized lab.

Side effects of combination therapy will be monitored and described according to Common Toxicity Criteria, version 4.0 (National Cancer Institute, USA).

The purpose of current study is to determine the clinical efficacy and tolerability of combination therapy of Dasatinib with multi-agent chemotherapy in newly-diagnosed Ph+ ALL.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Institute of Hematology & Blood Diseases Hospital

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 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients aged 18 to 60 years with De novo Philadelphia chromosome positive (Philadelphia chromosome positive or BCR/ABL transcript positive) acute lymphoblastic leukemia.
  2. Eastern Cooperative Oncology Group (ECOG) Performance status 2.
  3. Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum glutamic-oxaloacetic transaminase(SGOT) and serum glutamic pyruvic transaminase(SGPT) ≤ 2.5 x ULN; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; Patients must have adequate cardiac function (ejection fraction ≥ 45 % on Multiple Gated Acquisition (MUGA) scan).
  4. Patients must have the following laboratory values (≥ lower limit of normal (LLN) or corrected to within normal limits with supplements prior to the first dose of study medication.): Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN
  5. Patients should sign informed consent form.

Exclusion Criteria:

  1. Impaired cardiac function:

    Long QT syndrome or a known family history of long QT syndrome; clinically significant resting brachycardia (<50 beats per minute); ejection fraction < 45 % on MUGA scan. QTc interval > 450 msec on baseline ECG (using the QTcF formula). If QTcF interval>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc. Myocardial infarction within 12 months prior to starting study; other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension, uncontrolled arrhythmias).

    Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.

  2. Other concurrent severe and/or uncontrolled medical conditions:

    Patients with another primary malignant disease, except those that do not currently require treatment; acute or chronic liver, pancreatic or severe renal disease; another severe and/or life-threatening medical disease.

  3. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential).
  4. Who is known human deficiency virus (HIV) positive.
  5. Use of any other investigational agent in the last 30 days.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Dasatinib 100 mg per day will be given orally along with combination chemotherapy starting day 8 of induction chemotherapy. Dasatinib will be given continuously (if it's tolerable) for 2 years since achievement of complete remission (CR) as part of consolidation chemotherapy and maintenance therapy.Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT),or patients who keep BCR/ABL negative can receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy.
Drug: cyclophosphamide
Drug: prednisone
Drug: cytarabine
Drug: dexamethasone
Drug: etoposide
Drug: methotrexate
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: mercaptopurine
Procedure: autologous hematopoietic stem cell transplantation
Drug: daunorubicin
Drug: mitoxantrone
Drug: vincristine
Drug: Dasatinib
Second-generation tyrosine kinase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: From date of diagnosis until the date of death from any cause, assessed up to 60 months.
From date of diagnosis until the date of death from any cause, assessed up to 60 months.

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival (DFS)
Time Frame: From the date of complete remission(CR) until the date of documented relapse,assessed up to 60 months.
From the date of complete remission(CR) until the date of documented relapse,assessed up to 60 months.
The complete remission (CR) rate
Time Frame: Participants will be followed for the duration of the treatment, an expected average of 6 months.
Participants will be followed for the duration of the treatment, an expected average of 6 months.
The molecular CR rate
Time Frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Participants will be followed for the duration of the treatment, an expected average of 24 months.
The plasma level of dasatinib in the regimen
Time Frame: Up to 3 months.
Up to 3 months.
The Cerebrospinal fluid level of dasatinib in the regimen
Time Frame: Up to 6 months.
Up to 6 months.
Number of adverse event of combined treatment
Time Frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Participants will be followed for the duration of the treatment, an expected average of 24 months.
Grade of adverse event of combined treatment
Time Frame: Participants will be followed for the duration of the treatment, an expected average of 24 months.
Participants will be followed for the duration of the treatment, an expected average of 24 months.

Collaborators and Investigators

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

Sponsor

Institute of Hematology & Blood Diseases Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

August 1, 2015

Primary Completion (Actual)

December 31, 2021

Study Completion (Actual)

December 31, 2021

Study Registration Dates

First Submitted

August 5, 2015

First Submitted That Met QC Criteria

August 13, 2015

First Posted (Estimate)

August 14, 2015

Study Record Updates

Last Update Posted (Actual)

August 3, 2022

Last Update Submitted That Met QC Criteria

August 2, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IHBDH-IIT2015001

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.

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