Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
Brief summary
RATIONALE: Giving high-dose chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. An autologous stem cell transplant may be able to replace the blood-forming cells that were destroyed by the chemotherapy. PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide followed by an autologous stem cell transplant works in treating patients with multiple myeloma.
Detailed description
OBJECTIVES: Primary * To compare relapse-free survival and overall survival of patients with multiple myeloma treated with IV busulfan vs historical control patients treated with oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation. Secondary * To compare pulmonary toxicity rates of IV busulfan vs oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation. OUTLINE: Patients receive high-dose busulfan IV every 6 hours on days -8 to -4 and high-dose cyclophosphamide IV over 4 hours on days -3 and -2. Patients undergo autologous hematopoietic stem cell transplantation on day 0. After completion of study treatment, patients are followed up periodically.
Interventions
DRUGbusulfan
IV busulfan 0.8 mg/kg every 6 hours x 16 doses
DRUGcyclophosphamide
IV cyclophosphamide 60 mg/kg over 4 hours x 2 days
PROCEDUREautologous hematopoietic stem cell transplantation
infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of plasma cell myeloma * Patients with cardiac ejection fraction \>= 45% or clearance by Cleveland Clinic Faculty (CCF) cardiologist * Patients with diffusion capacity of carbon monoxide (DLCO) \>= 45% predicted or clearance by CCF pulmonologist * Patient with previously harvested peripheral blood progenitor cells with a minimum of 2 x 10\^6 CD 34+ cells/kg harvested
Exclusion criteria
* Patients receiving total body irradiation * Non-myeloablative/reduced-intensity conditioning * Pregnant and breast feeding patients * Human immunodeficiency virus (HIV) positive * Patients with serum creatinine \> 2.0 * Prior Hematopoietic Stem Cell (HSC) transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free Survival | at 6 months | Number of participants without progressive disease at the end of the study period, using the definitions for complete response, partial response and progressive disease from the International Myeloma Working Group . |
| Overall Survival | at 6 months | Number of patients alive at the end of the study period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Toxicity | At 6 months | Toxicity criteria will be assessed and graded according to the National Cancer Institute (NCI) Common Terminology Criteria (CTC) v3.0. Estimated using exact 95% binomial confidence intervals. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Busulfan Treatment busulfan: IV busulfan 0.8 mg/kg every 6 hours x 16 doses
cyclophosphamide: IV cyclophosphamide 60 mg/kg over 4 hours x 2 days
autologous hematopoietic stem cell transplantation: infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0 | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ineligible | 2 |
| Overall Study | Insurance denied participation | 11 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Busulfan Treatment |
|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 57 |
| serious Total, serious adverse events | 12 / 57 |
Outcome results
Primary
Overall Survival
Number of patients alive at the end of the study period
Time frame: at 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Busulfan Treatment | Overall Survival | 53 participants |
Primary
Relapse-free Survival
Number of participants without progressive disease at the end of the study period, using the definitions for complete response, partial response and progressive disease from the International Myeloma Working Group .
Time frame: at 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Busulfan Treatment | Relapse-free Survival | 48 participants |
Secondary
Pulmonary Toxicity
Toxicity criteria will be assessed and graded according to the National Cancer Institute (NCI) Common Terminology Criteria (CTC) v3.0. Estimated using exact 95% binomial confidence intervals.
Time frame: At 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Busulfan Treatment | Pulmonary Toxicity | 3.5 percentage of participants |