RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients with chronic myelogenous leukemia.

Condition	Treatment or Intervention	Phase
accelerated phase chronic myelogenous leukemia refractory chronic myelogenous leukemia chronic phase chronic myelogenous leukemia	Drug: busulfan  Drug: c-myb antisense oligodeoxynucleotide  Drug: cyclophosphamide  Drug: filgrastim	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the ability of c-myb antisense oligodeoxynucleotide to purge bone marrow cells of clonogenic chronic myelogenous leukemia tumor cells and repopulate the bone marrow with normal stem cells in patients treated with high-dose busulfan and cyclophosphamide followed by autologous bone marrow transplantation using marrow treated with c-myb antisense oligodeoxynucleotide. II. Determine the response rate, degree of hematopoietic reconstitution, overall survival, and relapse-free survival of these patients treated with this regimen. III. Determine the toxicity of this regimen in these patients.

PROTOCOL OUTLINE: Patients undergo bone marrow harvest. The bone marrow is treated with c-myb antisense oligodeoxynucleotide and cryopreserved. A portion of the marrow is cryopreserved untreated in case of engraftment failure. Patients receive oral busulfan every 6 hours on days -7 to -4 for a total of 16 doses. Patients receive cyclophosphamide IV over 1 hour on days -3 and -2. Bone marrow is reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily beginning on day 0 and continuing until blood counts recover. Patients are followed every 2-3 months for 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 18-24 months.

Ages Eligible for Study:  18 Years   -   60 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically and cytologically proven chronic myelogenous leukemia; Accelerated phase OR Chronic phase; Must have in vitro response to c-myb antisense oligodeoxynucleotide
• No hypocellular marrow (less than 25% cellularity)
• No patients under age 55 with a HLA-matched sibling donor

--Prior/Concurrent Therapy--

• Biologic therapy: At least 3 months since prior interferon therapy
• Chemotherapy: No prior busulfan
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 to 60
• Performance status: 0-1
• Hematopoietic: Granulocyte count greater than 1,000/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin less than 1.5 mg/dL; AST less than 3 times normal
• Renal: Creatinine less than 2.0 mg/dL; Creatinine clearance greater than 60 mL/min
• Cardiovascular: Left ventricular ejection fraction normal; No significant cardiac disease requiring digoxin, diuretics, antiarrhythmics, or antianginal medications
• Pulmonary: PFTs normal with normal DLCO
• Other: No persistent infection requiring antibiotics; No concurrent organ damage or medical problem that would preclude study; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

Pennsylvania
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104-4283,  United States

Study chairs or principal investigators

Selina M. Luger,  Study Chair,  University of Pennsylvania Cancer Center   

Study ID Numbers:  CDR0000063772; UPCC-3492; NCI-H94-0532
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002592
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08