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

February 19, 2008
March 25, 2013
October 2005
December 2008   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT00618501 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Imatinib Mesylate and Combination Chemotherapy With or Without a Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
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.

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.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
January 2009
December 2008   (final data collection date for primary outcome measure)

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
Both
15 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT00618501
CDR0000586176, AMC-UUCM-2005-0238, NOVARTIS-AMC-UUCM-2005-0238
Not Provided
Not Provided
Asan Medical Center
Not Provided
Principal Investigator: Kyoo H. Lee, MD Asan Medical Center
National Cancer Institute (NCI)
January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP