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

Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006244
• Other study ID #: 1461.00
• Secondary ID: NCI-2011-01313
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2000
• Last updated: June 1, 2016
• Start date: February 2000

Study information

• Verified date: June 2016
• 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

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

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 information / eligibility

• Status: Completed
• Enrollment: 36
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Stage I Multiple Myeloma
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• melphalan
Given IV

Biological:
• recombinant interferon alfa
Given SC
• aldesleukin
Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Procedure:
• in vitro-treated peripheral blood stem cell transplantation
Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		From baseline until disease progression, assessed up to 50 years	No
Primary	Initial response to therapy (complete response, partial response, or progression of disease)		2 years	No
Primary	Time to disease progression		From baseline until disease progression, assessed up to 50 years	No
Secondary	Number of patients experiencing grade 3-4 regimen related toxicity		From baseline until disease progression, assessed up to 50 years	Yes