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

NCT ID: NCT00003056

Last Updated: 2021-05-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-04-01
• Study Completion Date: 2003-06-01

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.

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.

Conditions

Leukemia; Lymphoma; Graft Versus Host Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE

Study Groups

Unselected peripheral blood haemopoietic stem cells (PBSC)

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

Group Type: ACTIVE_COMPARATOR

cyclosporine and methotrexate

Intervention Type: DRUG

CD34+ cells isolated from PBSC

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

Group Type: EXPERIMENTAL

cyclosporine

Intervention Type: DRUG

Interventions

cyclosporine

Intervention Type: DRUG

cyclosporine and methotrexate

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Los Angeles, California, United States

Jacksonville, Florida, United States

Atlanta, Georgia, United States

Indianapolis, Indiana, United States

Lawrence, Kansas, United States

Saint Paul, Minnesota, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

Hackensack, New Jersey, United States

Pittsburgh, Pennsylvania, United States

San Antonio, Texas, United States

Richmond, Virginia, United States

Adelaide, South Australia, Australia

Countries

United States; Australia

Other Identifiers

MCV-CCHR-9703-2A

Identifier Type: -

Identifier Source: secondary_id

CDR0000065709

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-G97-1311

Identifier Type: -

Identifier Source: secondary_id

BAXTER-302302

Identifier Type: -

Identifier Source: org_study_id