Prevention of Graft-Versus-Host Disease in Patients With Advanced Leukemia or Lymphoma Who Are Eligible for Peripheral Stem Cell Transplantation

Sponsor

Baxalta now part of Shire (Industry)

Overall Status

Terminated

CT.gov ID

NCT00003056

Collaborator

(none)

105

Enrollment

Locations

Arms

Actual Duration (Months)

8.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Graft Versus Host Disease	Drug: cyclosporine Drug: cyclosporine and methotrexate	Phase 3

Detailed Description

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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

105 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Primary Purpose:

Supportive Care

Official Title:

Peripheral Blood Stem Cell Transplantation in Patients With Advanced Malignancies Eligible for Allogeneic Transplantation From Matched Related Donors: A Randomized Study of Cyclosporine/Methotrexate or Cyclosporine/T-Cell Depletion (CD34 Cell Selection) for GVHD Prophylaxis

Actual Study Start Date :

Apr 1, 1997

Actual Primary Completion Date :

Jun 1, 2003

Actual Study Completion Date :

Jun 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Unselected peripheral blood haemopoietic stem cells (PBSC) Unselected PBSC together with control graft versus host disease (GVHD) prophylaxis - Control	Drug: cyclosporine and methotrexate
Experimental: CD34+ cells isolated from PBSC CD34+ cells isolated from PBSC using the Isolex 300i system together with cyclosporine	Drug: cyclosporine

Arm

Intervention/Treatment

Active Comparator: Unselected peripheral blood haemopoietic stem cells (PBSC)

Unselected PBSC together with control graft versus host disease (GVHD) prophylaxis - Control

Drug: cyclosporine and methotrexate

Experimental: CD34+ cells isolated from PBSC

CD34+ cells isolated from PBSC using the Isolex 300i system together with cyclosporine

Drug: cyclosporine

Outcome Measures

Primary Outcome Measures

Time to neutrophil engraftment [Month 1, post-transplant]
Time to neutrophil engraftment [Month 2, post-transplant]
Time to neutrophil engraftment [Month 3, post-transplant]
Time to neutrophil engraftment [Month 4, post-transplant]
Time to neutrophil engraftment [Month 5, post-transplant]
Time to neutrophil engraftment [Month 6, post-transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 human lymphocyte antigen (HLA)-identical related donor required No active central nervous system (CNS) or skin leukemia involvement No disease that requires additional mediastinal radiation

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 serum glutamate oxalo-acetate transaminase (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: diffusing capacity of the lung for carbon monoxide (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

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

Contacts and Locations

Locations

	City	State	Country
1	Los Angeles	California	United States
2	Jacksonville	Florida	United States
3	Atlanta	Georgia	United States
4	Indianapolis	Indiana	United States
5	Lawrence	Kansas	United States
6	Saint Paul	Minnesota	United States
7	Kansas City	Missouri	United States
8	Saint Louis	Missouri	United States
9	Hackensack	New Jersey	United States
10	Pittsburgh	Pennsylvania	United States
11	San Antonio	Texas	United States
12	Richmond	Virginia	United States
13	Adelaide	South Australia	Australia