Clinical trial NCT00349778: High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma
Official title: High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2006-07-10
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Pulmonary Toxicity
timeFrame: 2 years
Secondary outcomes:
measure: Overall Participant Survival (OS)
timeFrame: 5 years
measure: Number of Participants That Relapse After Autologous Transplantation
timeFrame: 5 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Sally Arai
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.