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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00618501
First received: February 19, 2008
Last updated: March 25, 2013
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: etoposide
Drug: imatinib mesylate
Drug: leucovorin calcium
Drug: methotrexate
Drug: prednisolone
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Procedure: allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Gleevec (Imatinib) Plus Multi-Agent Chemotherapy For Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients achieving hematologic and molecular complete response (CR) after induction chemotherapy and imatinib mesylate [ Designated as safety issue: No ]
  • Duration of hematologic CR [ Designated as safety issue: No ]
  • Durations of hematologic and molecular CR after hematopoietic stem cell transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Clinical toxicities [ Designated as safety issue: Yes ]
  • Prognostic factors in patients treated with this regimen [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: October 2005
Study Completion Date: January 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00618501

Locations
Korea, Republic of
Asan Medical Center - University of Ulsan College of Medicine
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Kyoo H. Lee, MD Asan Medical Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00618501     History of Changes
Other Study ID Numbers: CDR0000586176, AMC-UUCM-2005-0238, NOVARTIS-AMC-UUCM-2005-0238
Study First Received: February 19, 2008
Last Updated: March 25, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
untreated adult acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Cytarabine
Methotrexate
Imatinib
Daunorubicin
Etoposide
Prednisolone
Methylprednisolone Hemisuccinate
Vincristine
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Methylprednisolone acetate
Prednisolone acetate
Hydrocortisone
Methylprednisolone
Hydrocortisone-17-butyrate
Leucovorin

ClinicalTrials.gov processed this record on April 17, 2014