Imatinib Mesylate and Combination Chemotherapy With or Without a Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

March 25, 2013 updated by: Asan Medical Center

Gleevec (Imatinib) Plus Multi-Agent Chemotherapy For Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Imatinib mesylate may also stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known which treatment regimen is most effective in treating acute lymphoblastic leukemia.

PURPOSE: This phase II trial is studying the side effects of giving imatinib mesylate together with combination chemotherapy with or without a donor stem cell transplant and to see how well it works in treating patients with newly diagnosed acute lymphoblastic leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the clinical efficacy of imatinib mesylate and combination chemotherapy in terms of complete response (CR) rate (both hematologic and molecular), CR duration, and overall survival in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.
  • To determine the toxicities of this regimen in these patients.

Secondary

  • To establish the prognostic factors in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to age (64 or less vs 65 or over).

  • Induction chemotherapy: Patients receive daunorubicin hydrochloride IV continuously over 24 hours on days 1-3, vincristine IV on days 1 and 8, and oral prednisolone on days 1-14. Treatment repeats for 5 courses in the absence of disease progression or unacceptable toxicity.
  • Imatinib mesylate administration: Patients also receive oral imatinib mesylate once daily beginning on day 8 of course 1 induction chemotherapy and continuing for up to 2 years.
  • Consolidation chemotherapy: Patients receive daunorubicin hydrochloride IV continuously over 24 hours on days 1-2, vincristine IV on days 1 and 8, and oral prednisolone on days 1-14 in course 1; cytarabine IV over 2 hours and etoposide IV over 3 hours on days 1-4 in courses 2 and 4; and methotrexate IV continuously over 36 hours on days 1-2 and 15-16 and leucovorin calcium IV every 6 hours x 3 doses followed by oral leucovorin calcium until methotrexate levels are < 0.05 micromol/L in courses 3 and 5. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with available HLA-matched sibling or unrelated hematopoietic cell donors or HLA-nonidentical familial hematopoietic cell donors proceed to allogeneic hematopoietic stem cell transplantation (HSCT). Patients who are without hematopoietic cell donors and who remain in hematologic remission continue to receive maintenance therapy with oral imatinib mesylate.
  • Allogeneic HSCT: Patients undergo HSCT.
  • CNS prophylaxis: Patients receive six doses of intrathecal (IT) methotrexate and hydrocortisone beginning on the first day of each chemotherapy course. Patients with CNS disease at diagnosis receive intensified CNS therapy comprising 10 doses of IT methotrexate and cranial irradiation after bone marrow remission is achieved.

After completion of study treatment, patients are followed periodically.

Study Type

Interventional

Enrollment (Anticipated)

50

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

  • Korea, Republic of
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center - University of Ulsan College of Medicine

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

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Acute lymphoblastic leukemia (ALL) or acute mixed lineage leukemia

    • Newly diagnosed disease

    • Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia or Ph+ acute mixed lineage leukemia

      • Positive result for RT-PCR for Bcr-Abl transcript (Ph+ ALL or Philadelphia-chromosome positive acute mixed lineage leukemia)

PATIENT CHARACTERISTICS:

  • Bilirubin < 2 mg/dL
  • SGOT < 3 times upper limit of normal
  • Creatinine < 2.0 mg/dL
  • Ejection fraction > 45% by MUGA scan
  • Not nursing
  • Fertile patients must use effective contraception
  • No known sensitivity to study drugs
  • No severe medical conditions that, in the view of the investigator, prohibits participation in the study

PRIOR CONCURRENT THERAPY:

  • No other investigational agents in the past 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
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Proportion of patients achieving hematologic and molecular complete response (CR) after induction chemotherapy and imatinib mesylate
Duration of hematologic CR
Durations of hematologic and molecular CR after hematopoietic stem cell transplantation

Secondary Outcome Measures

Outcome Measure
Overall survival
Clinical toxicities
Prognostic factors in patients treated with this regimen

Collaborators and Investigators

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

Sponsor

Asan Medical Center

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

October 1, 2005

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

February 19, 2008

First Submitted That Met QC Criteria

February 19, 2008

First Posted (Estimate)

February 20, 2008

Study Record Updates

Last Update Posted (Estimate)

March 26, 2013

Last Update Submitted That Met QC Criteria

March 25, 2013

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000586176
  • AMC-UUCM-2005-0238
  • NOVARTIS-AMC-UUCM-2005-0238

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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