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

Primary Purpose

Leukemia, Lymphoma, Graft Versus Host Disease

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
cyclosporine
cyclosporine and methotrexate
Sponsored by
Baxalta now part of Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Leukemia focused on measuring recurrent adult diffuse small cleaved cell lymphoma, adult acute myeloid leukemia in remission, recurrent grade 2 follicular lymphoma, accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, recurrent grade 1 follicular lymphoma, recurrent adult lymphoblastic lymphoma, recurrent marginal zone lymphoma, chronic phase chronic myelogenous leukemia, recurrent small lymphocytic lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent adult immunoblastic large cell lymphoma, graft versus host disease, recurrent adult diffuse mixed cell lymphoma, recurrent mantle cell lymphoma, splenic marginal zone lymphoma, recurrent adult acute myeloid leukemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, recurrent adult diffuse large cell lymphoma, nodal marginal zone B-cell lymphoma, recurrent adult Burkitt lymphoma

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Unselected peripheral blood haemopoietic stem cells (PBSC)

CD34+ cells isolated from PBSC

Arm Description

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

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

Outcomes

Primary Outcome Measures

Time to neutrophil engraftment
Time to neutrophil engraftment
Time to neutrophil engraftment
Time to neutrophil engraftment
Time to neutrophil engraftment
Time to neutrophil engraftment

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
May 3, 2021
Sponsor
Baxalta now part of Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00003056
Brief Title
Prevention of Graft-Versus-Host Disease in Patients With Advanced Leukemia or Lymphoma Who Are Eligible for Peripheral Stem Cell Transplantation
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Terminated
Why Stopped
Interim analysis indicated study should be terminated
Study Start Date
April 1, 1997 (Actual)
Primary Completion Date
June 1, 2003 (Actual)
Study Completion Date
June 1, 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Graft Versus Host Disease
Keywords
recurrent adult diffuse small cleaved cell lymphoma, adult acute myeloid leukemia in remission, recurrent grade 2 follicular lymphoma, accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, recurrent grade 1 follicular lymphoma, recurrent adult lymphoblastic lymphoma, recurrent marginal zone lymphoma, chronic phase chronic myelogenous leukemia, recurrent small lymphocytic lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent adult immunoblastic large cell lymphoma, graft versus host disease, recurrent adult diffuse mixed cell lymphoma, recurrent mantle cell lymphoma, splenic marginal zone lymphoma, recurrent adult acute myeloid leukemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, recurrent adult diffuse large cell lymphoma, nodal marginal zone B-cell lymphoma, recurrent adult Burkitt lymphoma

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Allocation
Randomized
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Unselected peripheral blood haemopoietic stem cells (PBSC)
Arm Type
Active Comparator
Arm Description
Unselected PBSC together with control graft versus host disease (GVHD) prophylaxis - Control
Arm Title
CD34+ cells isolated from PBSC
Arm Type
Experimental
Arm Description
CD34+ cells isolated from PBSC using the Isolex 300i system together with cyclosporine
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
cyclosporine and methotrexate
Primary Outcome Measure Information:
Title
Time to neutrophil engraftment
Time Frame
Month 1, post-transplant
Title
Time to neutrophil engraftment
Time Frame
Month 2, post-transplant
Title
Time to neutrophil engraftment
Time Frame
Month 3, post-transplant
Title
Time to neutrophil engraftment
Time Frame
Month 4, post-transplant
Title
Time to neutrophil engraftment
Time Frame
Month 5, post-transplant
Title
Time to neutrophil engraftment
Time Frame
Month 6, post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Lawrence
State/Province
Kansas
Country
United States
City
Saint Paul
State/Province
Minnesota
Country
United States
City
Kansas City
State/Province
Missouri
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Hackensack
State/Province
New Jersey
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Adelaide
State/Province
South Australia
Country
Australia

12. IPD Sharing Statement

Learn more about this trial

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

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