Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2011 by National Cancer Institute (NCI)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00055874
First received: March 6, 2003
Last updated: August 9, 2013
Last verified: November 2011

March 6, 2003
August 9, 2013
June 2002
December 2016   (final data collection date for primary outcome measure)
  • Overall survival [ Designated as safety issue: No ]
  • Risk group-dependent survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Hematologic, cytogenetic, and molecular response rates [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00055874 on ClinicalTrials.gov Archive Site
  • Adverse drug effects [ Designated as safety issue: Yes ]
  • Quality of life [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
Treatment Optimization Trial in Chronic Myeloid Leukemia (CML) - Randomized Controlled Comparison of Imatinib vs. Imatinib/Interferon-alpha vs. Imatinib/Low-Dose AraC vs. Interferon-alpha Standard Therapy and Determination of the Role of Allografting in Newly Diagnosed Chronic Phase

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, imatinib mesylate may stop the growth of cancer cells by blocking the enzymes needed for cancer cell growth. Interferon alfa may interfere with the growth of cancer cells and slow the growth of cancer. 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 chronic phase chronic myelogenous leukemia.

PURPOSE: This randomized phase III trial is studying imatinib mesylate with or without interferon alfa or cytarabine to see how well it works compared with interferon alfa followed by donor stem cell transplant in treating patients with newly diagnosed chronic phase chronic myelogenous leukemia.

OBJECTIVES:

  • Compare the hematologic, cytogenetic, and molecular response rates in patients with newly diagnosed chronic phase chronic myelogenous leukemia treated with imatinib mesylate alone or with interferon alfa or low-dose cytarabine vs interferon alfa standard therapy.
  • Compare the group-dependent, progression-free and overall survival and time to progression in patients treated with these regimens.
  • Compare the efficacy of allogeneic stem cell transplantation vs imatinib mesylate-based therapy in patients eligible for transplantation.
  • Compare the efficacy of reduced-intensity conditioning vs standard conditioning in patients over 45 years of age.
  • Determine the time to and duration of hematologic, cytogenetic, and molecular responses and correlate these factors in patients treated with these regimens.
  • Compare the short- and long-term adverse effects of these regimens in these patients.
  • Compare the presentation, duration, and responses to therapy of accelerated and blastic phases in patients treated with these regimens.
  • Determine the survival of high-risk patients after early allografting.
  • Determine the influence of pre-transplantation therapies on the outcome of allogeneic stem cell transplantation in these patients.

OUTLINE: This is a randomized, multicenter, pilot study. Patients are stratified according to participating center. Patients with low- to intermediate-risk disease are randomized to 1 of 4 treatment arms. Patients with high-risk disease are randomized to 1 of 3 treatment arms with imatinib mesylate-based regimens.

  • Arm I: Patients receive oral imatinib mesylate once daily for up to 12 months in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral imatinib mesylate as in arm I. Patients also receive interferon alfa subcutaneously (SC) 3 times a week beginning at least 3 months after the start of imatinib mesylate.
  • Arm III: Patients receive oral imatinib mesylate as in arm I. Patients also receive cytarabine SC up to twice daily for 5 days monthly beginning at least 3 months after the start of imatinib mesylate.
  • Arm IV: After initial cytoreduction with hydroxyurea, patients receive interferon alfa SC daily with or without hydroxyurea. In the absence of a complete response after 3 months, patients may also receive low-dose cytarabine SC once daily. Treatment continues for up to 21 months.

Patients who fail interferon alfa therapy are crossed over to receive imatinib mesylate.

Patients who fail therapy with imatinib mesylate and are eligible for an allogeneic transplantation are stratified according to availability of donor (HLA-identical related vs unrelated), status, and participating center. Patients are randomized to receive an allogeneic transplantation or continue any salvage therapy.

Patients who are not eligible for allogeneic transplantation receive hydroxyurea and cytarabine or high-dose chemotherapy with autologous stem cell rescue followed by interferon- or imatinib mesylate-based therapy.

Patients over 45 years of age are further randomized to receive an age-adjusted standard conditioning regimen or reduced intensity preparative regimen (mini transplantation) prior to allogeneic transplantation.

Patients are followed every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,600 patients (400 per treatment arm) will be accrued for this study within 4-5 years.

Interventional
Phase 3
Allocation: Randomized
Primary Purpose: Treatment
Leukemia
  • Biological: recombinant interferon alfa
  • Drug: cytarabine
  • Drug: hydroxyurea
  • Drug: imatinib mesylate
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: autologous bone marrow transplantation
  • Procedure: peripheral blood stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1600
Not Provided
December 2016   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Newly diagnosed chronic phase chronic myelogenous leukemia (CML)

    • bcr-abl positive
    • No blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood
  • Availability of a HLA-identical sibling or unrelated donor

PATIENT CHARACTERISTICS:

Age

  • Any age

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No second malignancy requiring therapy
  • No evidence of disease-related symptoms or extramedullary disease (including hepatosplenomegaly)
  • No serious diseases that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior interferon

Chemotherapy

  • No prior chemotherapy other than hydroxyurea

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy

Surgery

  • Not specified

Other

  • Prior anagrelide allowed
  • No participation in another clinical trial
Both
Not Provided
No
Germany,   Switzerland
 
NCT00055874
III-MK-CML-IV, CDR0000271424, EU-20248
Not Provided
Not Provided
III. Medizinische Klinik Mannheim
Not Provided
Study Chair: Ruediger Hehlmann, MD III. Medizinische Klinik Mannheim
National Cancer Institute (NCI)
November 2011

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