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
  Purpose

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.


Condition Intervention Phase
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
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Adverse drug effects [ Designated as safety issue: Yes ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 1600
Study Start Date: June 2002
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00055874

  Show 66 Study Locations
Sponsors and Collaborators
III. Medizinische Klinik Mannheim
Investigators
Study Chair: Ruediger Hehlmann, MD III. Medizinische Klinik Mannheim
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00055874     History of Changes
Other Study ID Numbers: III-MK-CML-IV, CDR0000271424, EU-20248
Study First Received: March 6, 2003
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
chronic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic myelogenous leukemia, BCR-ABL1 positive

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Imatinib
Interferon-alpha
Interferons
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014