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

Phase 2

Completed

Conditions: Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma

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

Registration Number: NCT00006244

Lead Sponsor: Fred Hutchinson Cancer Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (immunotherapy)	aldesleukin	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.
Treatment (immunotherapy)	in vitro-treated peripheral blood stem cell transplantation	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.
Treatment (immunotherapy)	melphalan	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.
Treatment (immunotherapy)	recombinant interferon alfa	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity	First 100 days post-transplant	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.
Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity	First 100 days post-transplant	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.