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

NCT02523976 | Completed Phase 2

• 1 other identifier: IIT2015001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute,Leukemia, Lymphoid

Keywords

Acute; Leukemia; Lymphoid; Philadelphia chromosome; dasatinib

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  From date of diagnosis until the date of death from any cause, assessed up to 60 months.

Secondary Outcomes (7)

• Disease-free survival (DFS)

  From the date of complete remission(CR) until the date of documented relapse,assessed up to 60 months.

• The complete remission (CR) rate

  Participants will be followed for the duration of the treatment, an expected average of 6 months.

• The molecular CR rate

  Participants will be followed for the duration of the treatment, an expected average of 24 months.

• The plasma level of dasatinib in the regimen

  Up to 3 months.

• The Cerebrospinal fluid level of dasatinib in the regimen

  Up to 6 months.

Study Arms (1)

Arm A

EXPERIMENTAL

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: Dasatinib; Drug: prednisone; Drug: cyclophosphamide; Drug: daunorubicin; Drug: vincristine; Drug: cytarabine; Drug: mercaptopurine; Drug: methotrexate; Drug: dexamethasone; Drug: mitoxantrone; Drug: etoposide; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: autologous hematopoietic stem cell transplantation

Interventions

Dasatinib DRUG

Second-generation tyrosine kinase inhibitor

Arm A

prednisone DRUG

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etoposide DRUG

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cyclophosphamide DRUG

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daunorubicin DRUG

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vincristine DRUG

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cytarabine DRUG

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mercaptopurine DRUG

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methotrexate DRUG

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dexamethasone DRUG

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mitoxantrone DRUG

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allogeneic hematopoietic stem cell transplantation PROCEDURE

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autologous hematopoietic stem cell transplantation PROCEDURE

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Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients aged 18 to 60 years with De novo Philadelphia chromosome positive (Philadelphia chromosome positive or BCR/ABL transcript positive) acute lymphoblastic leukemia.
• Eastern Cooperative Oncology Group (ECOG) Performance status 2.
• 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).
• 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
• Patients should sign informed consent form.

You may not qualify if:

• 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.
• 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.
• 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).
• Who is known human deficiency virus (HIV) positive.
• Use of any other investigational agent in the last 30 days.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (2)

• Gong X, Li L, Wei H, Liu B, Zhou C, Zhang G, Liu K, Lin D, Gong B, Wei S, Li Y, Mi Y, Wang Y, Wang J. A Higher Dose of Dasatinib May Increase the Possibility of Crossing the Blood-brain Barrier in the Treatment of Patients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia. Clin Ther. 2021 Jul;43(7):1265-1271.e1. doi: 10.1016/j.clinthera.2021.05.009. Epub 2021 Jun 10.

  PMID: 34120773 DERIVED

• Zhang GJ, Gong XY, Qiu SW, Zhou CL, Liu KQ, Lin D, Liu BC, Wei H, Wei SN, Li Y, Gu RX, Gong BF, Liu YT, Fang QY, Mi YC, Wang Y, Wang JX. [Dasatinib combined with multi-agent chemotherapy regimen in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a prospective study from a single center]. Zhonghua Xue Ye Xue Za Zhi. 2021 Feb 14;42(2):109-115. doi: 10.3760/cma.j.issn.0253-2727.2021.02.004. Chinese.

  PMID: 33858040 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Philadelphia Chromosome

Interventions

Dasatinib; Prednisone; Cyclophosphamide; Daunorubicin; Vincristine; Cytarabine; Mercaptopurine; Methotrexate; Dexamethasone; Mitoxantrone; Etoposide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Translocation, Genetic; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Purines; Aminopterin; Pterins; Pteridines; Pregnadienetriols; Steroids, Fluorinated; Anthraquinones; Anthrones; Anthracenes; Quinones; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Jianxiang Wang, Dr.

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2015
• First Posted: August 14, 2015
• Study Start: August 1, 2015
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 11, 2026

Record last verified: 2022-08

Locations

CN (1)