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Donor White Blood Cell Infusions and Interleukin-2 in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Relapsed Advanced Lymphoid Cancer

Primary Purpose

Graft Versus Host Disease, Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
aldesleukin
therapeutic allogeneic lymphocytes
melphalan
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring graft versus host disease, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following advanced lymphoid malignancies: Multiple myeloma, meeting both of the following criteria: Deletion of chromosome 13 Elevated pre-transplant lactic dehydrogenase Chronic lymphocytic leukemia (CLL) Failed ≥ 2 prior conventional chemotherapy regimens, including fludarabine Small lymphocytic lymphoma Follicular non-Hodgkin's lymphoma Received ≥ 3 prior conventional chemotherapy regimens Mantle cell lymphoma Received ≥ 3 prior conventional chemotherapy regimens Predicted poor outcome and relapsed disease after undergoing autologous stem cell transplantation ≥ 6 months ago Measurable disease, defined as any evidence of disease by scans or blood or urine analysis At least 8 x 10^6 autologous CD34-positive cells/kg available for transplantation Stem cell mobilization allowed Haploidentical related donor available Sex-mismatched Identical for 1 HLA haplotype AND mismatched for ≥ 1 HLA-A, -B, -C, or DRB1 locus of the unshared haplotype No HLA-identical related or unrelated donor available Not eligible for first-line autologous stem cell transplantation on protocol FHCRC-1368.00, FHCRC-1366.00, FHCRC-1461.00, or FHCRC-1595.00 No bulky disease, defined as total volume of all measurable tumor > 500 cc No CNS disease resistant to therapy PATIENT CHARACTERISTICS: Age 18 to 69 Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Liver function tests or liver enzymes ≤ 2 times upper limit of normal Renal Not specified Cardiovascular Ejection fraction ≥ 45% No symptomatic cardiac disease Pulmonary DLCO ≥ 50% Other Not pregnant or nursing Fertile patients must use effective contraception HIV Negative No active infection PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No prior allogeneic stem cell transplantation Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other No concurrent contrast dye during and for 3 weeks after completion of interleukin-2 administration

Sites / Locations

  • Seattle Cancer Care Alliance
  • Fred Hutchinson Cancer Research Center

Outcomes

Primary Outcome Measures

Feasibility
Toxicity

Secondary Outcome Measures

Extent, degree, and duration of donor chimerism
Complete response rate

Full Information

First Posted
November 3, 2005
Last Updated
September 20, 2010
Sponsor
Fred Hutchinson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00248430
Brief Title
Donor White Blood Cell Infusions and Interleukin-2 in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Relapsed Advanced Lymphoid Cancer
Official Title
A Phase I-II Trial of Adoptive Immunotherapy Using Haploidentical, Related Donor-Lymphocyte Infusions and IL-2 After Autologous Stem Cell Transplantation for Advanced Lymphoid Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2010
Overall Recruitment Status
Completed
Study Start Date
August 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. An autologous stem cell transplant using the patient's stem cells may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving white blood cells from a donor may help the patient's body destroy any remaining cancer cells. Interleukin-2 may stimulate the white blood cells to kill cancer cells. PURPOSE: This phase I/II trial is studying the side effects of donor white blood cell infusions and interleukin-2 and to see how well they work in treating patients who are undergoing an autologous stem cell transplant for relapsed advanced lymphoid cancer.
Detailed Description
OBJECTIVES: Primary Determine the feasibility and toxicity of haploidentical related donor lymphocyte infusions (DLI) and interleukin-2, in terms of acute graft-versus-host-disease, graft failure, and transplant-related mortality, in patients with relapsed advanced lymphoid malignancies undergoing autologous stem cell transplantation. Secondary Determine the extent, degree, and duration of donor chimerism in patients treated with this regimen. Determine, preliminarily, activity of haploidentical DLI, as measured by complete response rate, in these patients. OUTLINE: This is a pilot study. Patients receive high-dose melphalan IV over 15-60 minutes on day -2 and undergo autologous stem cell transplantation on day 0. Patients receive haploidentical related donor lymphocyte infusions (DLI) IV on days 1, 5*, and 10* and interleukin-2 (IL-2) IV continuously on days 1-12. NOTE: *DLI are not administered on days 5 or 10 if grade 3 or 4 graft-versus-host disease is present After completion of study treatment, patients are followed monthly for 3 months and then every 3-12 months thereafter. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
Keywords
graft versus host disease, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
aldesleukin
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Procedure
Intervention Name(s)
bone marrow ablation with stem cell support
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Primary Outcome Measure Information:
Title
Feasibility
Title
Toxicity
Secondary Outcome Measure Information:
Title
Extent, degree, and duration of donor chimerism
Title
Complete response rate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following advanced lymphoid malignancies: Multiple myeloma, meeting both of the following criteria: Deletion of chromosome 13 Elevated pre-transplant lactic dehydrogenase Chronic lymphocytic leukemia (CLL) Failed ≥ 2 prior conventional chemotherapy regimens, including fludarabine Small lymphocytic lymphoma Follicular non-Hodgkin's lymphoma Received ≥ 3 prior conventional chemotherapy regimens Mantle cell lymphoma Received ≥ 3 prior conventional chemotherapy regimens Predicted poor outcome and relapsed disease after undergoing autologous stem cell transplantation ≥ 6 months ago Measurable disease, defined as any evidence of disease by scans or blood or urine analysis At least 8 x 10^6 autologous CD34-positive cells/kg available for transplantation Stem cell mobilization allowed Haploidentical related donor available Sex-mismatched Identical for 1 HLA haplotype AND mismatched for ≥ 1 HLA-A, -B, -C, or DRB1 locus of the unshared haplotype No HLA-identical related or unrelated donor available Not eligible for first-line autologous stem cell transplantation on protocol FHCRC-1368.00, FHCRC-1366.00, FHCRC-1461.00, or FHCRC-1595.00 No bulky disease, defined as total volume of all measurable tumor > 500 cc No CNS disease resistant to therapy PATIENT CHARACTERISTICS: Age 18 to 69 Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Liver function tests or liver enzymes ≤ 2 times upper limit of normal Renal Not specified Cardiovascular Ejection fraction ≥ 45% No symptomatic cardiac disease Pulmonary DLCO ≥ 50% Other Not pregnant or nursing Fertile patients must use effective contraception HIV Negative No active infection PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No prior allogeneic stem cell transplantation Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other No concurrent contrast dye during and for 3 weeks after completion of interleukin-2 administration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William I. Bensinger, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States

12. IPD Sharing Statement

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Donor White Blood Cell Infusions and Interleukin-2 in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Relapsed Advanced Lymphoid Cancer

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