RATIONALE: Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Anti-thymocyte globulin and cyclosporine may prevent this from happening.

PURPOSE: Randomized clinical trial to study the effectiveness of combining anti-thymocyte globulin with cyclosporine in preventing graft-versus-host disease in patients who are undergoing chemotherapy with or without radiation therapy followed by donor stem cell transplantation for acute lymphoblastic leukemia or acute myeloid leukemia.

Condition

Treatment or Intervention

adult acute lymphoblastic leukemia adult acute myeloid leukemia Graft Versus Host Disease secondary acute myeloid leukemia

Drug: anti-thymocyte globulin  Drug: busulfan  Drug: cyclophosphamide  Drug: cyclosporine  Procedure: allogeneic bone marrow transplantation  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy  Procedure: supportive care/therapy

OBJECTIVES: Primary

• Compare the incidence of acute graft-vs-host disease (GVHD) within the first 100 days after transplantation in patients with acute lymphoblastic leukemia or acute myeloid leukemia treated with a myeloablative conditioning regimen comprising cyclophosphamide (with or without radiotherapy) and low- vs high-dose anti-thymocyte globulin followed by allogeneic HLA-matched related stem cell transplantation and cyclosporine.
• Compare the incidence of serious adverse events within the first 100 days after transplantation in patients treated with these regimens.

Secondary

• Compare 100-day and 6-month survival in patients treated with these regimens.
• Compare the severity of acute GVHD in patients treated with these regimens.
• Compare the incidence of culture-proven infections at 100 days and 6 months after transplantation in patients treated with these regimens.
• Compare the incidence of mucositis, in terms of presence, severity, and duration, in patients treated with these regimens.
• Compare the number of days on opiate drugs within the first 30 days after transplantation in patients treated with these regimens.
• Compare the time to engraftment in patients treated with these regimens.
• Compare the incidence of hospitalization within the first 6 months after transplantation, in terms of length of initial stay, cumulative total days, and number of hospitalizations, in patients treated with these regimens.
• Compare the relapse rate and time to relapse in patients treated with these regimens.
• Compare the incidence and severity of chronic GVHD between 100 days and 6 months after transplantation in patients treated with these regimens.

OUTLINE: This is a pilot, randomized, open-label, multicenter study.

• Conditioning: All patients receive a standard myeloablative-conditioning regimen that contains cyclophosphamide IV over 2 hours per center regimen, typically on days -6 to -3. Patients also undergo total body irradiation OR receive busulfan.
• Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive low-dose anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
• Arm II: Patients receive high-dose anti-thymocyte globulin IV over 4-8 hours on days -5 to -1.
• Allogeneic hematopoietic stem cell transplantation: Patients in both arms undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
• Post-transplantation GVHD prophylaxis: Patients in both arms receive cyclosporine IV over 1-4 hours or orally twice daily beginning on day -1 and continuing until approximately day 60 followed by tapering doses until day 180 in the absence of GVHD. Patients are followed at 7, 14, 21, 30, 100, and 180 days.

PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of acute myeloid leukemia (AML) or acute lymphoblastic leukemia
• In first complete remission or second complete remission
• Secondary AML allowed
• HLA-A, -B, and –DRB1 identical related donor available AND must be fully matched at Class II by high-resolution molecular HLA typing (at least 4 digits)
• Currently receiving a myeloablative conditioning regimen that includes cyclophosphamide
• All patients from a center should receive the same conditioning regimen throughout the study
• No fludarabine or other purine analogues (e.g. cladribine or pentostatin) as part of conditioning regimen
• No uncontrolled CNS disease

PATIENT CHARACTERISTICS: Age

• 18 to 55

Performance status

• ECOG 0-3

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin < 2 mg/dL
• ALT and/or AST ≤ 3 times normal

Renal

• Creatinine < 2.0 mg/dL OR
• Creatinine clearance > 50 mL/min

Cardiovascular

• Ejection fraction > 40%
• No severe cardiac disease

Other

• Negative pregnancy test
• Fertile patients must use effective contraception
• No known contraindication to administration of rabbit anti-thymocyte globulin
• No current drug or alcohol abuse
• No significant medical or psychosocial problem or unstable disease state (including, but not limited to, morbid obesity) that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior or concurrent bone marrow transplantation from a donor who has positive serology for HIV, hepatitis B virus, hepatitis C virus, or syphilis
• No IV immunoglobulin prior to engraftment
• No concurrent ex vivo engineered or processed graft (CD34+ enrichment or T-cell depletion)

Chemotherapy

• See Disease Characteristics
• No prior or concurrent methotrexate for graft-vs-host disease prophylaxis

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 30 days since prior experimental agents
• No other concurrent investigational agents
• Enrollment in investigational studies (i.e., anti-microbial agents) allowed only for life threatening events or after exhausting other treatment modalities

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1678,  United States; Recruiting

Study chairs or principal investigators

Gary John Schiller, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000389241; UCLA-0402009-01; GENZ-SMC-101-1026
Record last reviewed:  September 2004
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093587
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-29