RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. PURPOSE: Randomized phase III trial to compare the effectiveness of cyclosporine plus methotrexate with cyclosporine plus T cell depletion for prevention of graft-versus-host disease during peripheral stem cell transplantation in patients who have advanced leukemia or lymphoma who are eligible for transplanted peripheral stem cells from a donor.

Condition	Treatment or Intervention	Phase
Lymphoma Leukemia	Drug: cyclosporine  Drug: methotrexate	Phase III

Further Study Details: 

OBJECTIVES: I. Demonstrate that the graft versus host disease (GVHD) prophylactic regimen consisting of T-cell depletion and cyclosporine results in less toxicity than the control regimen of methotrexate and cyclosporine in recipients of peripheral blood stem cell transplants. II. Monitor safety of the two regimens in order to assure that the treatment regimen dose not result in any increase in serious or unexpected toxicities, does not compromise the efficacy of GVHD prophylaxis, and does not compromise the efficacy of the disease therapy.

PROTOCOL OUTLINE: This is a multicenter, controlled, randomized trial. Patients are assigned to high or low risk groups and randomized to the control or treatment arms. Patients are stratified by risk group and by site. Mobilization, apheresis, and successful cryopreservation of the minimum number of CD34 cells for transplant has to be achieved prior to initiating cytoreductive therapy. Following intensive cytoreductive therapy, patients receive either unselected peripheral blood stem cells (PBSC) together with the control graft versus host disease (GVHD) prophylaxis regimen or CD34+ cells isolated from PBSC with cyclosporine. In the control group, GVHD prophylaxis consists of two drug therapies, cyclosporine and methotrexate. The cyclosporine is administered first by IV continuous infusion and then later orally, twice a day, in decreasing increments for 180 days. Methotrexate is administered by IV on days 1, 3, 6, and 11. Cyclosporine is discontinued after day +180 if there is no evidence of GVHD. In the treatment group, GVHD prophylaxis consists of T cell depletion of the transplant product using the Isolex positive selection procedure (Isolex selected CD34+ cells) and cyclosporine. The cyclosporine is administered at the same doses and increments as in the control group. In cases where there still is acute or chronic GVHD, the patient is given the appropriate salvage regimens. Patients are followed monthly for 6 months after transplant, and then for 2 years to monitor relapses.

PROJECTED ACCRUAL: There will be 200 patients accrued (100 in each arm) in this study.

Ages Eligible for Study:  18 Years   -   55 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Acute lymphocytic leukemia (ALL) with documented chemosensitivity (complete response [CR], partial response [PR], or minor response [MR]) in first or second remission, first or second relapse, or high risk ALL with Ph positive 9/22 translocation OR Acute myelogenous leukemia (AML) with documented chemosensitivity (CR, PR, or MR) in first or second remission, or first or second relapse; OR Chronic myelogenous leukemia (CML), chronic or accelerated, that is not in blast crisis; OR Hodgkin's disease or non-Hodgkin's lymphoma with documented chemosensitivity in first or second relapse
• Consenting HLA-identical related donor required
• No active CNS or skin leukemia involvement
• No disease that requires additional mediastinal radiation

--Prior/Concurrent Therapy--

• No more that 2 prior therapy regimens
• Biologic therapy: No prior autologous or allogeneic bone marrow or peripheral blood stem cell transplant
• Chemotherapy: Not specified
• Endocrine therapy: Not specified
• Radiotherapy: Prior radiation therapy subject to dose requirements
• Surgery: Not specified
• Other: At least 2 weeks since intravenous treatment with antifungal, antibacterial or antiviral agents, except for treatment of coagulase negative staphylococcal infection of an IV or central line

--Patient Characteristics--

• Age: 18-55
• Performance status: Karnofsky 70-100%
• Life expectancy: Greater than 8 weeks
• Hematopoietic: Not specified
• Hepatic: Bilirubin less than 1.5 times normal; SGOT less than 2 times normal
• Renal: Creatinine less than 1.5 times normal
• Cardiovascular: Left ventricular ejection fraction at rest at least 40% or within normal range
• Pulmonary: DLCO greater than 45% of predicted or within normal range
• Other: HIV negative; At least 2 weeks since any active infection requiring intravenous treatment with antifungal, antibacterial or antiviral agents with the exception of coagulase negative staphylococcal line infection; No coexisting medical problems that would significantly increase the risk of the transplant procedure; Not pregnant or nursing

New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
Virginia
      Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States

Study chairs or principal investigators

Saul Yanovich,  Study Chair,  Massey Cancer Center   

Study ID Numbers:  CDR0000065709; MCV-CCHR-9703-2A; NCI-G97-1311; BAXTER-302302
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003056
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08