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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: aldesleukin
* Biological: therapeutic allogeneic lymphocytes
* Drug: melphalan
* Procedure: bone marrow ablation with stem cell support
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: therapeutic allogeneic lymphocytes|nan|
|Drug: melphalan|nan|
|Procedure: bone marrow ablation with stem cell support|nan|
|Procedure: peripheral blood stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility |  |  | 
| Toxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent, degree, and duration of donor chimerism |  |  | 
| Complete response rate |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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