RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by peripheral stem cell transplantation and biological therapy in treating patients who have chronic myelogenous leukemia.

Condition	Treatment or Intervention	Phase
accelerated phase chronic myelogenous leukemia chronic phase chronic myelogenous leukemia refractory chronic myelogenous leukemia	Drug: busulfan  Drug: interferon alfa  Drug: interleukin-2  Drug: interleukin-2/sargramostim  Drug: sargramostim	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the toxicity of high-dose busulfan followed by interleukin-2 (IL-2) and sargramostim (GM-CSF) activated autologous/syngeneic peripheral blood stem cell (PBSC) transplantation, sequential IL-2 and GM-CSF therapy, and interferon alfa in patients with chronic myelogenous leukemia. II. Determine engraftment potential of IL-2/GM-CSF activated PBSC followed by sequential IL-2/GM-CSF therapy in this patient population. III. Assess the time to cytogenetic and/or morphologic relapse, overall event-free survival, and overall survival in these patients treated with this regimen.

PROTOCOL OUTLINE: Autologous peripheral blood stem cells (PBSC) are harvested and activated with interleukin-2 (IL-2) and sargramostim (GM-CSF) on another protocol. Patients receive oral busulfan every 6 hours on days -6 to -3 for a total of 16 doses. IL-2 and GM-CSF-activated PBSC are reinfused on day 0. Beginning 4 hours after PBSC infusion, patients receive IL-2 IV continuously for 5 days followed by 2 days of rest for 4 weeks. In addition, GM-CSF is administered subcutaneously (SC) every Monday, Wednesday, and Friday for 4 weeks. Upon hematologic recovery, but no earlier than 2 weeks after IL-2 and GM-CSF, patients receive interferon alfa SC 3 times weekly until clear evidence of disease progression. Patients are followed every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 2-3 years.

Ages Eligible for Study:  up to  70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Chronic myelogenous leukemia with previously stored CD34 cells from FHCRC-928.00; Chronic phase: No evidence of a major response after 6-month course of interferon alfa OR Initially achieved a major cytogenetic response but subsequently failed interferon alfa OR Accelerated phase: At least 1 month after collection of peripheral blood stem cells
• No blast crisis
• No CNS involvement
• Ineligible for or refused allogeneic conventional or minitransplant protocol

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics
• Chemotherapy: Not specified
• Endocrine therapy: No concurrent ongoing steroids
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: 70 and under
• Performance status: Karnofsky 80-100%
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2.0 mg/dL (unless history of Gilbert's disease); AST or ALT no greater than 2.5 times upper limit of normal; No cirrhosis; Hepatitis B and C negative
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: No myocardial infarction within past 12 months; No unstable angina, poorly controlled arrhythmias, or hypertension; LVEF greater than 50%
• Pulmonary: DLCO at least 50%; Alveolar arterial gradient less than 30 at sea level
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; HIV negative; No active infection requiring systemic antibiotics; No known allergy to gentamicin or murine or E. coli proteins or documented prior anaphylactic reaction to sargramostim (GM-CSF) or interleukin-2

Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80010,  United States
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States

Study chairs or principal investigators

Leona Holmberg,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000067877; FHCRC-1455.00; NCI-G00-1792
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00005948
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08