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

NCT00006244 | Completed Phase 2 Results

• 2 other identifiers: 1461.00NCI-2011-01313
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity

  First 100 days post-transplant

• Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity

  First 100 days post-transplant

Study Arms (1)

Treatment (immunotherapy)

EXPERIMENTAL

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; Biological: recombinant interferon alfa; Biological: aldesleukin; Procedure: in vitro-treated peripheral blood stem cell transplantation

Interventions

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Treatment (immunotherapy)

recombinant interferon alfa BIOLOGICAL

Given SC

Also known as: Alferon N, alpha interferon, IFN-A, Intron A, Roferon-A

Treatment (immunotherapy)

aldesleukin BIOLOGICAL

Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Treatment (immunotherapy)

in vitro-treated peripheral blood stem cell transplantation PROCEDURE

Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Also known as: 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

Treatment (immunotherapy)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Interferon-alpha; Interferon Alfa-n3; Introns; Interferon alpha-2; aldesleukin; Interleukin-2; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Interleukins; Lymphokines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Leona A. Holmberg
• Organization: Fred Hutchinson Cancer Research Center

lholmber@fredhutch.org

206-667-6447

Study Officials

• Leona Holmberg

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2000
• First Posted: January 27, 2003
• Study Start: February 1, 2000
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 12, 2017
• Results First Posted: May 16, 2017

Record last verified: 2017-06

Locations

US (1)