Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
Brief summary
RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may kill more cancer cells.\> PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with newly diagnosed multiple myeloma.
Detailed description
OBJECTIVES: Primary \* Assess the response rate in patients with newly diagnosed active multiple myeloma treated with lenalidomide, cyclophosphamide, and dexamethasone. Secondary * Assess the toxicity of this regimen in these patients. * Determine the time to progression in patients treated with this regimen. OUTLINE: Patients receive oral lenalidomide on days 1-21, oral cyclophosphamide on days 1, 8, and 15, and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4-12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for up to 5 years.
Interventions
DRUGcyclophosphamide
300 mg/m2 administrated by PO (with food)on Days 1, 8, 15 (up to 12 cycles) OR 300 mg administrated by PO (with food)on Days 1, 8, 15 (up to 12 cycles)
DRUGdexamethasone
40 mg administrated by PO (with food)on Days 1, 8, 15 & 22
DRUGlenalidomide
25 mg administrated by PO (with food)on Days 1-21
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
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
DISEASE CHARACTERISTICS: * Diagnosis of multiple myeloma * Newly diagnosed disease * Symptomatic disease * Measurable or evaluable disease, defined by ≥ 1 of the following criteria: * Serum monoclonal protein ≥ 1.0 g by protein electrophoresis * Monoclonal protein \> 200 mg by 24-hour urine electrophoresis * Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio * Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease) * Measurable soft tissue plasmacytoma not previously irradiated * No monoclonal gammopathy of undetermined significance or smoldering myeloma PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-2 (ECOG PS 3 allowed if secondary to pain) * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 75,000/mm\^3 * Hemoglobin ≥ 8.0 g/dL * Creatinine ≤ 2.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective double-method contraception (1 highly effective and 1 additional method) for 1 month before, during, and for 4 weeks after completion of study therapy * No uncontrolled infection * No other active malignancy * No other malignancies within the past 5 years except for currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast * No NYHA class III-IV congestive heart failure * No untreated active deep vein thrombosis PRIOR CONCURRENT THERAPY: * At least 3 weeks since prior radiotherapy for solitary plasmacytoma * Prior clarithromycin, therapeutic dehydroepiandrosterone (DHEA), anakinra, pamidronate disodium, or zoledronic acid allowed * No prior cytotoxic chemotherapy * No prior corticosteroids (except for treatment of a nonmalignant disorder) * Concurrent corticosteroids (prednisone ≤ 20 mg/per day) allowed * No concurrent radiotherapy except palliative radiotherapy for a single painful bone lesion or fracture
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment | Duration of Treatment (up to 5 years) | Response that was confirmed on 2 consecutive evaluations during treatment * Complete Response(CR): Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & \<5% plasma cells in bone marrow (BM) * Very Good Partial Response(VGPR): \>=90% reduction in serum M-component; Urine M-Component \<100 mg per 24 hours; \<=5% plasma cells in BM * Partial Response PR): \>= 50% reduction in serum M-Component and/or Urine M-Component \>= 90% reduction or \<200 mg per 24 hours; or \>= 50% decrease in difference between involved and uninvolved FLC levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 5 years | OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method. |
| Progression-free Survival (PFS) | up to 5 years | PFS was defined as the time from registration to progression or death due to any cause. The median PFS with 95%CI was estimated using the Kaplan Meier method.\> Progression was defined as any one or more of the following:\> An increase of 25% from lowest confirmed response in:\> * Serum M-component (absolute increase \>= 0.5g/dl)\> * Urine M-component (absolute increase \>= 200mg/24hour\> * Difference between involved and uninvolved Free Light Chain levels (absolute increase \>= 10mg/dl\> * Bone marrow plasma cell percentage (absolute increase of \>=10%) |
| Duration of Response (DOR) | up to 5 years | Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. The median DOR with 95%CI was estimated using the Kaplan Meier method. |
Countries
United States
Participant flow
Recruitment details
Fifty-three (53) participants were recruited between July 2006 and August 2008 at Mayo Clinic.
Participants by arm
| Arm | Count |
|---|---|
| LCD (Cyclophosphamide 300 mg/m^2) Lenalidomide 25 mg PI days 1-21 Cyclophosphamide 300 mg/m\^2 PO days 1, 8, 15 Dexamethasone 40 mg PI days 1, 8, 15, 22 | 34 |
| LCD (Cyclophosphamide 300 mg) Lenalidomide 25 mg PI days 1-21 Cyclophosphamide 300 mg PO days 1, 8, 15 Dexamethasone 40 mg PI days 1, 8, 15, 22 | 19 |
| Total | 53 |
Baseline characteristics
| Characteristic | Total | LCD (Cyclophosphamide 300 mg/m^2) | LCD (Cyclophosphamide 300 mg) |
|---|---|---|---|
| Age Continuous | 64 years | 63.5 years | 65 years |
| Durie Salmon Stage Stage IA - Low Cell Mass | 4 paricipants | 3 paricipants | 1 paricipants |
| Durie Salmon Stage Stage IIA - Intermediate Cell Mass | 18 paricipants | 7 paricipants | 11 paricipants |
| Durie Salmon Stage Stage IIIA/B - High Cell Mass | 31 paricipants | 24 paricipants | 7 paricipants |
| Parameter of Hematologic Response - Bone Marrow Plasma Cells > 30% No | 22 participants | 17 participants | 5 participants |
| Parameter of Hematologic Response - Bone Marrow Plasma Cells > 30% Yes | 31 participants | 17 participants | 14 participants |
| Parameter of Hematologic Response - Serum Immunoglobulin Free Light Chain >= 10 mg/dL No | 18 participants | 13 participants | 5 participants |
| Parameter of Hematologic Response - Serum Immunoglobulin Free Light Chain >= 10 mg/dL Yes | 35 participants | 21 participants | 14 participants |
| Parameter of Hematologic Response - Serum M-spike >= 1 g/dL No | 14 participants | 9 participants | 5 participants |
| Parameter of Hematologic Response - Serum M-spike >= 1 g/dL Yes | 39 participants | 25 participants | 14 participants |
| Parameter of Hematologic Response - Urine M-Spike >= 200 mg/24 hours No | 37 participants | 23 participants | 14 participants |
| Parameter of Hematologic Response - Urine M-Spike >= 200 mg/24 hours Yes | 16 participants | 11 participants | 5 participants |
| Region of Enrollment United States | 53 participants | 34 participants | 19 participants |
| Sex: Female, Male Female | 26 Participants | 17 Participants | 9 Participants |
| Sex: Female, Male Male | 27 Participants | 17 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 34 | 19 / 19 |
| serious Total, serious adverse events | 13 / 34 | 2 / 19 |
Outcome results
Primary
Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment
Response that was confirmed on 2 consecutive evaluations during treatment * Complete Response(CR): Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & \<5% plasma cells in bone marrow (BM) * Very Good Partial Response(VGPR): \>=90% reduction in serum M-component; Urine M-Component \<100 mg per 24 hours; \<=5% plasma cells in BM * Partial Response PR): \>= 50% reduction in serum M-Component and/or Urine M-Component \>= 90% reduction or \<200 mg per 24 hours; or \>= 50% decrease in difference between involved and uninvolved FLC levels
Time frame: Duration of Treatment (up to 5 years)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCD (Cyclophosphamide 300 mg/m^2) | Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment | 28 participants |
| LCD (Cyclophosphamide 300 mg) | Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment | 16 participants |
Secondary
Duration of Response (DOR)
Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. The median DOR with 95%CI was estimated using the Kaplan Meier method.
Time frame: up to 5 years
Population: Participants who achieved a partial response(PR) or better were evaluable for this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LCD (Cyclophosphamide 300 mg/m^2) | Duration of Response (DOR) | 26.1 months |
| LCD (Cyclophosphamide 300 mg) | Duration of Response (DOR) | NA months |
Secondary
Overall Survival (OS)
OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.
Time frame: up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LCD (Cyclophosphamide 300 mg/m^2) | Overall Survival (OS) | NA months |
| LCD (Cyclophosphamide 300 mg) | Overall Survival (OS) | NA months |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from registration to progression or death due to any cause. The median PFS with 95%CI was estimated using the Kaplan Meier method.\> Progression was defined as any one or more of the following:\> An increase of 25% from lowest confirmed response in:\> * Serum M-component (absolute increase \>= 0.5g/dl)\> * Urine M-component (absolute increase \>= 200mg/24hour\> * Difference between involved and uninvolved Free Light Chain levels (absolute increase \>= 10mg/dl\> * Bone marrow plasma cell percentage (absolute increase of \>=10%)
Time frame: up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LCD (Cyclophosphamide 300 mg/m^2) | Progression-free Survival (PFS) | 27 months |
| LCD (Cyclophosphamide 300 mg) | Progression-free Survival (PFS) | NA months |