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

Sponsor

Asan Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00618501

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Jan 1, 2009

Outcome Measures

Primary Outcome Measures

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

Overall survival []
Clinical toxicities []
Prognostic factors in patients treated with this regimen []

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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