RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Oblimersen may help imatinib mesylate kill more cancer cells by making cancer cells more sensitive to the drug.

PURPOSE: Phase II trial to study the effectiveness of combining oblimersen with imatinib mesylate in treating patients who have chronic myelogenous leukemia that has not responded to previous treatment with imatinib mesylate.

Condition	Treatment or Intervention	Phase
Philadelphia chromosome positive chronic myelogenous leukemia chronic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia	Drug: imatinib mesylate  Drug: oblimersen  Procedure: antisense therapy  Procedure: chemosensitization/potentiation  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the cytogenetic response rate of patients with imatinib mesylate-resistant chronic myelogenous leukemia treated with oblimersen and imatinib mesylate.
• Determine the hematologic and molecular response rate and duration of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oblimersen IV continuously on days 1-10 and oral imatinib mesylate once or twice daily. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without a hematologic response after 2 courses go off study. Patients with complete or partial response after 4 courses may continue to receive oral imatinib mesylate daily.

Patients in cohort 2 receive an escalated dose of oblimersen; if well tolerated, subsequent cohorts receive oblimersen at the higher dose with the original dose of imatinib mesylate. If oblimersen is not well tolerated in cohort 2, subsequent cohorts receive the original dose of oblimersen with an escalated dose of imatinib mesylate. The first 6 patients accrued continue to receive the original dose (dose taken prior to study) of imatinib mesylate throughout the study.

Patients are followed monthly for 3 months and then every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 12-43 patients will be accrued for this study within 6 months.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia in chronic phase
• Refractory to prior imatinib mesylate by the following criteria:
• At least 400 mg/day for more than 8 weeks without a complete hematologic response or more than 6 months without a major cytogenetic response
• No evidence of disease progression to accelerated or blast phases
• Must have received stable dose (at least 600 mg/day) of imatinib mesylate for at least 4 weeks without grade 2 or greater toxic effects
• If Philadelphia chromosome t(9;22) or a variant translocation is not detectable, then patients must meet 1 of the following:
• Polymerase chain reaction positive fusion transcripts for BCR/ABL
• BCR/ABL translocation present by fluorescence in situ hybridization
• Must also be registered on CLB-9665 and CLB-29801

PATIENT CHARACTERISTICS: Age

• 15 and over

Performance status

• Not specified

Life expectancy

• At least 2 years

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2 mg/dL
• AST no greater than 1.5 times upper limit of normal (ULN)
• PTT no greater than 1.5 times ULN

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No uncontrolled cardiovascular disease

Pulmonary

• No pulmonary disease that would preclude study participation

Other

• No other concurrently active malignancy except nonmelanoma skin cancer (i.e., completed therapy and considered to be at less than 30% risk of relapse within 1 year)
• No diabetes
• No infection
• No other serious illness that would limit life expectancy
• No psychiatric condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for at least 3 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior stem cell transplantation
• At least 4 weeks since prior interferon

Chemotherapy

• At least 4 weeks since prior hydroxyurea, homoharringtonine, or cytarabine
• No other prior antineoplastic agents (e.g., busulfan)
• No concurrent chemotherapy

Endocrine therapy

• No concurrent hormones except for steroids for adrenal failure or drug-related rash or hormones for nondisease-related conditions (e.g., insulin for diabetes or estrogens for osteopenia)

Radiotherapy

• No concurrent palliative radiotherapy

Surgery

• No concurrent surgical splenectomy except for traumatic injury, unresponsive infarction, emergency management, or splenic hemorrhage

Other

• At least 4 weeks since prior investigational agents
• At least 4 weeks since prior anagrelide
• No concurrent oral anticoagulants

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States
District of Columbia
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States
Illinois
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Indiana
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
Nevada
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States
New York
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
North Carolina
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Lenoir Memorial Cancer Center, Kinston,  North Carolina,  28503-1678,  United States
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States
Texas
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States

Study chairs or principal investigators

Meir Wetzler, MD,  Study Chair,  Roswell Park Cancer Institute   

Study ID Numbers:  CDR0000257816; CALGB-10107; NCT00049192
Record last reviewed:  April 2005
Last Updated:  April 5, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049192
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08