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

Immunotherapy for Autologous/Syngeneic Peripheral Blood Stem Cell (PBSC) Transplant Patients as Treatment for Advanced Multiple Myeloma

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

Study Overview

• Status: Completed
• Conditions: Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Refractory Multiple Myeloma
• Intervention / Treatment: Drug: melphalan; Biological: recombinant interferon alfa; Biological: aldesleukin; Procedure: in vitro-treated peripheral blood stem cell transplantation

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: melphalan; Given IV; Other Names: Alkeran; CB-3025; L-PAM; L-phenylalanine mustard; L-Sarcolysin; Biological: recombinant interferon alfa; Given SC; Other Names: Roferon-A; Intron A; alpha interferon; IFN-A; Alferon N; Biological: aldesleukin; Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion; Other Names: Proleukin; IL-2; recombinant human interleukin-2; recombinant interleukin-2; Procedure: in vitro-treated peripheral blood stem cell transplantation; Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion; Other Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival in Multiple Myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2 and interferon maintenance.	12.9 Median Years
Initial Response to Therapy	Evaluate initial response to therapy (complete remission, partial remission, stable response, or progression of disease)	Evaluated at Day +84-90 Post-Transplant
Time to Disease Progression		12.9 years (median)
Proportion of Patients Alive and in Remission		12.9 Median Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity	Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by younger (< 56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.	First 100 days post-transplant
Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity	Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by older (≥56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.	First 100 days post-transplant

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: February 1, 2000
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: September 11, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: June 16, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Interferons; Interferon-alpha; Aldesleukin; Interferon alpha-2; Melphalan; Interleukin-2
• Other Study ID Numbers: 1461.00; NCI-2011-01313 (Registry Identifier: CTRP (Clinical Trial Reporting Program))