Multiple Myeloma
Conditions
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.
Interventions
DRUGCyclophosphamide
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
DRUGEtoposide
100 mg etoposide as 5 mL solution in clear ampules for injection.
DRUGMelphalan
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.
DRUGCarmustine
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.
DRUGFilgrastim
Filgrastim in vials of 300 µg or 480 µg at a concentration of 300 µg/mL, to be given as a daily subcutaneous injection.
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pulmonary Toxicity | 2 years | Pulmonary toxicity was assessed as the incidence of interstitial pneumonitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Participant Survival (OS) | 5 years | Survival status was assessed 5 years after transplant. |
| Number of Participants That Relapse After Autologous Transplantation | 5 years | Relapse was measured as the number of patients who relapse after high-dose sequential therapy then autologous transplantation |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Sequential Therapy Cyclophosphamide + Etoposide + Melphalan + Carmustine with Filgrastim | 102 |
| Total | 102 |
Baseline characteristics
| Characteristic | High-Dose Sequential Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 91 Participants |
| Ethnicity (NIH/OMB) Ethnicity Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Ethnicity Not Hispanic or Latino | 85 Participants |
| Ethnicity (NIH/OMB) Ethnicity Unknown or Not Reported | 7 Participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 22 / 102 |
| other Total, other adverse events | 0 / 102 |
| serious Total, serious adverse events | 5 / 102 |
Outcome results
Primary
Number of Participants With Pulmonary Toxicity
Pulmonary toxicity was assessed as the incidence of interstitial pneumonitis.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-Dose Sequential Therapy | Number of Participants With Pulmonary Toxicity | 32 Participants |
Secondary
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
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-Dose Sequential Therapy | Number of Participants That Relapse After Autologous Transplantation | 66 Participants |
Secondary
Overall Participant Survival (OS)
Survival status was assessed 5 years after transplant.
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-Dose Sequential Therapy | Overall Participant Survival (OS) | 52 Participants |