Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma
Brief summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with cyclophosphamide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with cyclophosphamide works in treating patients with high risk, refractory, or relapsed multiple myeloma.
Detailed description
OBJECTIVES: * Determine the effect of rituximab and high-dose cyclophosphamide on the growth of myeloma stem cells in patients with high-risk, refractory, or relapsed multiple myeloma. OUTLINE: Patients receive rituximab IV on days -10 and -7; once weekly for 4 weeks (after completion of high-dose cyclophosphamide); and then once in months 3, 6, 9, and 12. Patients also receive high-dose cyclophosphamide on days -3 to 0. PROJECTED ACCRUAL: Not specified.
Interventions
BIOLOGICALrituximab
DRUGcyclophosphamide
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of multiple myeloma, meeting 1 of the following criteria: * High-risk disease in first remission, as defined by the following: * Beta-2 microglobulin \> 5.0 mg/dL * Chromosome 13 deletion * Primary refractory disease * Relapsed disease after achieving a response to prior chemotherapy * The following diagnoses are not allowed: * POEMS syndrome * Plasma cell leukemia * Amyloidosis * Nonsecretory myeloma * No evidence of spinal cord compression PATIENT CHARACTERISTICS: Age * Over 18 Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * Not pregnant or nursing * Fertile patients must use effective contraception * HIV negative * Has good organ function * Is in good physical condition * No active infection requiring antibiotics * No other malignancy within the past 2 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * No persistently detectable donor cells after prior allogeneic stem cell transplantation * No prior rituximab Chemotherapy * See Disease Characteristics Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * At least 28 days since prior therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival | 1 year | Percentage of study participants who did not report that their multiple myeloma relapsed or progressed (got worse) |
| Safety of Maintenance Rituximab Following High Dose Cyclophosphamide | 2, 3, 6, 9, and 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety and Toxicity | 2, 3, 6, 9, and 12 months |
| Complete Response (CR) Rate and Partial Response (PR) Rate | 1 year |
| Effect of Rituximab by Clonogenic Growth of Multiple Myeloma (MM) Progenitors and the Mechanisms by Which MM Stem Cells Are Inhibited | 2, 3, 6, 9, and 12 months |
| Overall Survival | 5 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab + Cyclophosphamide Rituximab 375 mg/m\^2 on Days -10 and -7; Cyclophosphamide 50 mg/kg on days -3, -2, -1, and 0; Rituximab 375 mg/m\^2 weekly x4 after platelet counts recover; For patients achieving at least stable disease, rituximab maintenance 375 mg/m\^2 once each during months 3, 6, 9, and 12 | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Rituximab + Cyclophosphamide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 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 | 15 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Event-free Survival
Percentage of study participants who did not report that their multiple myeloma relapsed or progressed (got worse)
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Cyclophosphamide | Event-free Survival | 29 percentage of participants |
Primary
Safety of Maintenance Rituximab Following High Dose Cyclophosphamide
Time frame: 2, 3, 6, 9, and 12 months
Secondary
Complete Response (CR) Rate and Partial Response (PR) Rate
Time frame: 1 year
Secondary
Effect of Rituximab by Clonogenic Growth of Multiple Myeloma (MM) Progenitors and the Mechanisms by Which MM Stem Cells Are Inhibited
Time frame: 2, 3, 6, 9, and 12 months
Secondary
Overall Survival
Time frame: 5 years
Secondary
Safety and Toxicity
Time frame: 2, 3, 6, 9, and 12 months