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

NCT ID: NCT00349778

Last Updated: 2017-12-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-31

Study Completion Date

2010-04-30

Brief Summary

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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

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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.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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High-Dose Sequential Therapy

Cyclophosphamide + Etoposide + Melphalan + Carmustine with Filgrastim

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

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

Etoposide

Intervention Type DRUG

100 mg etoposide as 5 mL solution in clear ampules for injection.

Melphalan

Intervention Type DRUG

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.

Carmustine

Intervention Type DRUG

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.

Filgrastim

Intervention Type DRUG

Filgrastim in vials of 300 µg or 480 µg at a concentration of 300 µg/mL, to be given as a daily subcutaneous injection.

Interventions

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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

Intervention Type DRUG

Etoposide

100 mg etoposide as 5 mL solution in clear ampules for injection.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Cytoxan Neosar Etopophos VePesid Toposar VP-16 Etoposide phosphate Alkeran L-PAM L-Sarcolysin Phenylalanine mustard BiCNU BCNU Neupogen Granulocyte-colony stimulating factor (G-CSF)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Sally Arai

Assistant Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sally Arai

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Stanford University School of Medicine

Stanford, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 21602899 (View on PubMed)

Other Identifiers

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97115

Identifier Type: OTHER

Identifier Source: secondary_id

BMT183

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-05704

Identifier Type: -

Identifier Source: org_study_id