Melphalan, Peripheral Stem Cell Transplantation, and Interleukin-2 Followed by Interferon Alfa in Treating Patients With Advanced Multiple Myeloma

NCT ID: NCT00006244

Last Updated: 2017-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-29
• Study Completion Date: 2016-04-30

Brief Summary

This phase II trial studies the effectiveness of melphalan, peripheral stem cell transplantation, and interleukin-2 followed by interferon alfa in treating patients who have advanced multiple myeloma (MM). Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Interleukin-2 (IL2) may stimulate a person's white blood cells to kill multiple myeloma cells. Interferon alfa may interfere with the growth of cancer cells

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate initial response to therapy, time to disease progression, and overall survival in MM patients treated with melphalan, IL2- incubated peripheral blood stem cells, and sequential IL2.

SECONDARY OBJECTIVES:

I. Evaluate grade 3-4 toxicities encountered by younger (< 56 years old) and older (>56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.

OUTLINE:

Patients receive melphalan intravenously (IV) over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa subcutaneously (SC) 3 times a week in the absence of disease progression or unacceptable toxicity.

Conditions

Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (immunotherapy)

Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

melphalan

Intervention Type: DRUG

Given IV

recombinant interferon alfa

Intervention Type: BIOLOGICAL

Given SC

aldesleukin

Intervention Type: BIOLOGICAL

Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

in vitro-treated peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Interventions

melphalan

Given IV

Intervention Type: DRUG

recombinant interferon alfa

Given SC

Intervention Type: BIOLOGICAL

aldesleukin

Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Intervention Type: BIOLOGICAL

in vitro-treated peripheral blood stem cell transplantation

Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Intervention Type: PROCEDURE

Other Intervention Names

Alkeran; CB-3025; L-PAM; L-phenylalanine mustard; L-Sarcolysin; Alferon N; alpha interferon; IFN-A; Intron A; Roferon-A; IL-2; Proleukin; recombinant human interleukin-2; recombinant interleukin-2; in vitro-treated PBPC transplantation; in vitro-treated PBSC; in vitro-treated peripheral blood progenitor cell transplantation; PBPC transplantation, in vitro-treated; peripheral blood progenitor cell transplantation, in vitro-treated

Eligibility Criteria

Inclusion Criteria

• Patient must be less than 70 years old
• Patients with advanced Multiple Myeloma that meet the eligibility requirements for mobilization/debulking with Cytoxan/VP-16/G-CSF, Cytoxan/Taxol/G-CSF, or Cytoxan/G-CSF (according to protocol 506.03); if clinically indicated a lower dose of cytoxan than 4g/m2 may be used for mobilization based on the attending's discretion; also, if the patients had previously collected PBSC of sufficient number in the past and meet the other eligibility requirements, they may be entered on this study after approval by the PI
• Patients with advanced Multiple Myeloma that have an identical syngeneic twin for donation of PBSCs
• Patients have advanced Multiple Myeloma if they were diagnosed initially with stage II or III disease or had stage I disease that progressed after initial therapy or failed to respond to therapy
• Syngeneic Donor Inclusion:

• Donor and patient have adequate documentation that donor and recipient are syngeneic; including ABO typing, HLA typing and VNTR studies
• Donor > 20 kg
• Donor meets eligibility to donate according to Standard Practice Guidelines

Exclusion Criteria

• Patient's age >= 70
• Karnofsky score less than 80
• A left ventricular ejection fraction less than 50%; Patients with congestive heart disease, history of myocardial infarction (MI), coronary artery disease or any arrhythmia history
• Total bilirubin > 1.5 mg/ml (unless history of Gilbert's disease)
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 2 x upper limit of normal
• Estimated creatinine clearance < 60 ml/min or creatinine serum > 2.0 mg/dl
• Pregnancy
• Seropositivity for human immunodeficiency virus
• Patients who cannot give informed consent
• Secondary malignancies other than basal cell carcinoma of the skin or carcinoma in situ within the last five years
• History of seizures or requirement for medicines, such as haldol, for controlling mental disorders
• Concurrent need for corticosteroid therapy
• Active connective tissue disease
• Pleural effusion, pericardial effusion or ascites
• Patients allergic to gentamicin
• Patients with positive PCR for hepatitis C or hepatitis B
• Patients with hypersensitivity to E. coli - derived preparations
• Patients with systemic infection at time of IL2 therapy
• Patients who previously have had more than 50% of their pelvic area irradiated
• Patients with pulmonary function tests that show diffusion capacity (corrected) < 60%, and/or forced expiratory volume in 1 second (FEV1) < 65% of predicted

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Leona Holmberg

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Leona Holmberg

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Other Identifiers

NCI-2011-01313

Identifier Type: REGISTRY

Identifier Source: secondary_id

1461.00

Identifier Type: -

Identifier Source: org_study_id