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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00618501
• Other study ID #: CDR0000586176
• Secondary ID: AMC-UUCM-2005-02
• Status: Completed
• Phase: Phase 2
• First received: February 19, 2008
• Last updated: March 25, 2013
• Start date: October 2005
• Est. completion date: January 2009

Study information

• Verified date: January 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• cytarabine

• daunorubicin hydrochloride

• etoposide

• imatinib mesylate

• leucovorin calcium

• methotrexate

• prednisolone

• therapeutic hydrocortisone

• vincristine sulfate

Procedure:
• allogeneic hematopoietic stem cell transplantation

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center - University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients achieving hematologic and molecular complete response (CR) after induction chemotherapy and imatinib mesylate			No
Primary	Duration of hematologic CR			No
Primary	Durations of hematologic and molecular CR after hematopoietic stem cell transplantation			No
Secondary	Overall survival			No
Secondary	Clinical toxicities			Yes
Secondary	Prognostic factors in patients treated with this regimen			No