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

Sponsored by:	Fred Hutchinson Cancer Research Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00248430

Purpose

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.

Condition	Intervention	Phase
Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm	Drug: aldesleukin Drug: melphalan Drug: therapeutic allogeneic lymphocytes Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation	Phase I Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma

Drug Information available for: Melphalan Aldesleukin Melphalan hydrochloride Sarcolysin Interleukin-2

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Feasibility [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Extent, degree, and duration of donor chimerism [ Designated as safety issue: No ]
Complete response rate [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	August 2003

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.

Eligibility

Ages Eligible for Study:	18 Years to 69 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00248430

Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

Investigators

Principal Investigator:

William I. Bensinger, MD

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000430694, FHCRC-1838.00
Study First Received:	November 3, 2005
Last Updated:	November 16, 2008
ClinicalTrials.gov Identifier:	NCT00248430
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Melphalan
Leukemia, Lymphoid
Blood Protein Disorders
Graft versus host disease
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Paraproteinemias
Hemostatic Disorders
Leukemia
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Chronic lymphocytic leukemia
Immunoproliferative Disorders

Hematologic Diseases
Leukemia, B-cell, chronic
Blood Coagulation Disorders
Vascular Diseases
Mantle cell lymphoma
Recurrence
Multiple Myeloma
Homologous wasting disease
Lymphatic Diseases
Aldesleukin
Interleukin-2
Graft vs Host Disease
Lymphoproliferative Disorders
Follicular lymphoma
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplasms
Anti-HIV Agents
Neoplasms by Histologic Type
Anti-Retroviral Agents
Immune System Diseases

Antineoplastic Agents
Therapeutic Uses
Cardiovascular Diseases
Antiviral Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009