RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of high-dose chemotherapy plus peripheral stem cell transplantation in treating patients with chronic myelogenous or acute leukemia.

Condition	Treatment or Intervention	Phase
Leukemia, Myeloid Leukemia, Myeloid, Chronic	Drug: busulfan  Drug: cyclophosphamide  Drug: cyclosporine  Drug: decitabine  Drug: filgrastim  Drug: methotrexate  Drug: methylprednisolone  Drug: tacrolimus	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of decitabine in combination with busulfan and cyclophosphamide in patients with hematologic malignancies.

II. Establish the pharmacokinetics of decitabine and busulfan in this patient population.

III. Determine the effectiveness of this combination in achieving durable complete remission in patients with chronic myelogenous leukemia (CML) in blast crisis or acute myelogenous leukemia (AML) in relapse undergoing allogeneic stem cell transplantation.

PROTOCOL OUTLINE: In cohorts of 3, patients receive escalating doses of decitabine (DAC) IV over 4 hours on days -8 and -7. Busulfan is administered orally q 6 hours on consecutive days -6 through -4. Cyclophosphamide is given IV over 1 hour on consecutive days -3 and -2. The maximum tolerated dose of DAC is defined as the dose at which 2 patients experience dose limiting toxicity.

Donors receive filgrastim SQ daily q 12 hours starting 2-4 days prior to the first stem cell collection and before DAC infusion. Leukapheresis is conducted daily. If insufficient number of cells are collected, blood marrow is harvested for supplementation. Stem cells are infused on day 0.

For graft vs host disease prophylaxis (GVHD), patients receive tacrolimus IV beginning one day before stem cell infusion, then orally following tolerance to tacrolimus. Patients intolerant to tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment. All patients receive methylprednisolone given according to clinical grade of GVHD procedures.

For CNS prophylaxis, methotrexate is given intrathecally or intraventricularly monthly, beginning on the second month through the eighth month of treatment.

Allogeneic patients are followed until the end of 1 year.

PROJECTED ACCRUAL: An estimated 30 allogeneic recipients will be recruited in 2 years for the expected study duration of 2-3 years.

Ages Eligible for Study:  15 Years   -   55 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Acute leukemia past first remission or induction failure
• Chronic myelogenous leukemia in accelerated phase or blast crisis

--Prior/Concurrent Therapy--

• Not specified

--Patient Characteristics--

• Age: 15 to 55
• Performance status: Zubrod 0-2
• Life expectancy: Life expectancy not severely limited by concurrent illness
• Hematopoietic: Not specified
• Hepatic: No evidence of chronic active hepatitis or cirrhosis; Bilirubin no greater than 2 times upper limit of normal; SGPT no greater than 4 times upper limit of normal
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: Left ventricular ejection fraction at least 50%; No uncontrolled arrhythmias or symptomatic cardiac disease
• Pulmonary: FEV1, FVC, and DLCO at least 50%; No symptomatic pulmonary disease
• Other: Related donor who is HLA-identical required; No effusion or ascites greater than 1 L prior to drainage; HIV negative; Not pregnant; No active CNS disease

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030,  United States

Study chairs or principal investigators

Sergio Giralt,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000065033; MDA-DM-94064; NCI-G96-0999
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002831
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08