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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00248430
• Other study ID #: 1838.00
• Secondary ID: FHCRC-1838.00CDR
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 3, 2005
• Last updated: September 20, 2010
• Start date: August 2003
• Est. completion date: July 2007

Study information

• Verified date: September 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Biological:
• aldesleukin

• therapeutic allogeneic lymphocytes

Drug:
• melphalan

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility			No
Primary	Toxicity			Yes
Secondary	Extent, degree, and duration of donor chimerism			No
Secondary	Complete response rate			No