High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma

This study uses a sequence of high-dose chemotherapy drugs and a stem cell transplant to treat multiple myeloma. The study is being performed to evaluate the efficacy and side effects of treatment. Specifically, the study is designed to reduce the risk of interstitial pneumonitis.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Etoposide; Drug: Melphalan; Drug: Carmustine; Drug: Filgrastim

Detailed Description

Analysis of 196 previously treated patients demonstrated a median event-free survival (EFS) of 36 months with a median overall survival of more than 6 years. The main toxicity of this therapy is related to carmustine-induced pneumonitis or interstitial pneumonitis (IP). This complication is related to the dose of carmustine. Institutional experience in myeloma patients using this dose of carmustine indicates an incidence of IP of34%.

There have been recent studies evaluating the role of tandem autologous transplants for patients with multiple myeloma. These trials were based upon the hypothesis that performing tandem high-dose therapy regimens would lead to increased tumor cell kill, decreased tumor burden and an improvement in overall survival. Our results with high-dose sequential therapy including the dose-intense carmustine/melphalan transplant demonstrates similar median EFS and overall survival (OS) when compared with the results of tandem transplant approaches.The proposed trial will continue to use a high-dose sequential transplant approach, however, we will use a reduced dose of carmustine which we expect to be associated with a lower incidence of IP.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

• Stage II to III multiple myeloma, or progression after initial treatment of Stage I disease; early or relapsed
• Age 18 to 75 years.
• Pathology reviewed and the diagnosis confirmed at Stanford University Medical Center.
• Patients with amyloidosis may be eligible for this trial, with approval by the Principle Investigator.
• Patients must have a Karnofsky performance status > 70%.
• Aspartate aminotransferase (AST) must be < 2 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) must be < 2 x ULN
• Total bilirubin < 2 mg/dL.
• Serum creatinine < 2.0 or 24-hour creatinine clearance ≥ 60 mL/min.
• Patients must be HIV-negative.
• Patients must provide signed, informed consent.

EXCLUSION CRITERIA

• Severe psychological or medical illness
• Prior autologous hematopoietic cell transplantation
• Pregnant
• Lactating women
• Smoldering multiple myeloma,
• Monoclonal gammopathy of unknown significance or primary amyloidosis will be excluded from this study

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: High-Dose Sequential Therapy; Cyclophosphamide + Etoposide + Melphalan + Carmustine with Filgrastim

Drug: Cyclophosphamide; Cyclophosphamide as a white powder in 100 mg, 200 mg and 500 mg vials, to be dissolved in ~250 mL of saline or D5W and infused IV over 2 hours; Other Names: Cytoxan; Neosar; Drug: Etoposide; 100 mg etoposide as 5 mL solution in clear ampules for injection.; Other Names: Toposar; VP-16; Etopophos; Etoposide phosphate; VePesid; Drug: Melphalan; Melphalan as single-use glass vials of freeze-dried melphalan hydrochloride (equivalent to 50 mg of melphalan), to be reconstituted in 0.9% sodium chloride solution to not greater than 0.45 mg/mL, and administered within 1 hour of constitution.; Other Names: Phenylalanine mustard; Alkeran; L-PAM; L-Sarcolysin; Drug: Carmustine; Carmustine as a powder for reconstitution in 100 mg vials, to be reconstituted with 3 mL sterile dehydrated ethanol and D5W. Carmustine should be dissolved in 500 mL of 5% dextrose in water (D5W) and infused IV over 2 hours.; Other Names: BCNU; BiCNU; Drug: Filgrastim; Filgrastim in vials of 300 µg or 480 µg at a concentration of 300 µg/mL, to be given as a daily subcutaneous injection.; Other Names: Neupogen; Granulocyte-colony stimulating factor (G-CSF)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Pulmonary Toxicity	Pulmonary toxicity was assessed as the incidence of interstitial pneumonitis.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Participant Survival (OS)	Survival status was assessed 5 years after transplant.	5 years
Number of Participants That Relapse After Autologous Transplantation	Relapse was measured as the number of patients who relapse after high-dose sequential therapy then autologous transplantation	5 years

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Sally Arai, Stanford University

Publications and helpful links

General Publications

• Chen AI, Negrin RS, McMillan A, Shizuru JA, Johnston LJ, Lowsky R, Miklos DB, Arai S, Weng WK, Laport GG, Stockerl-Goldstein K. Tandem chemo-mobilization followed by high-dose melphalan and carmustine with single autologous hematopoietic cell transplantation for multiple myeloma. Bone Marrow Transplant. 2012 Apr;47(4):516-21. doi: 10.1038/bmt.2011.106. Epub 2011 May 23.

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: July 5, 2006
• First Submitted That Met QC Criteria: July 5, 2006
• First Posted (Estimate): July 10, 2006

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 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; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Adjuvants, Immunologic; Cyclophosphamide; Etoposide; Etoposide phosphate; Lenograstim; Melphalan; Carmustine
• Other Study ID Numbers: IRB-05704; 97115 (Other Identifier: Stanford University Alternate IRB Approval Number); BMT183 (Other Identifier: OnCore number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No