Multiple Myeloma
Conditions
Keywords
primary systemic amyloidosis
Brief summary
RATIONALE: Drugs such as CC-5013 and dexamethasone may be effective in treating primary systemic amyloidosis. PURPOSE: This phase II trial is studying CC-5013 to see how well it works with or without dexamethasone in treating patients with primary systemic amyloidosis.
Detailed description
OBJECTIVES: Primary * Determine the tolerability of CC-5013 in patients with primary systemic (AL) amyloidosis. * Determine the objective hematologic response rate in patients treated with this drug. * Determine amyloid organ disease response in patients treated with this drug. Secondary * Determine hematologic and amyloid organ disease response in patients who do not achieve a response to CC-5013 alone and are subsequently treated with CC-5013 and dexamethasone. * Determine the toxicity of CC-5013 in combination with dexamethasone in these patients. OUTLINE: Patients receive oral CC-5013 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients not achieving a hematologic response continue to receive CC-5013 as before and also receive oral dexamethasone twice daily on days 1-4, 9-12, and 17-20 of every other 28-day course for up to 6 courses of combination therapy. Patients who maintain a hematologic response after 6 courses of combination therapy may receive CC-5013 alone in the absence of disease progression or unacceptable toxicity. Patients not achieving a hematologic response after the initiation of dexamethasone are removed from the study. Patients are followed annually. PROJECTED ACCRUAL: A total of 15-25 patients will be accrued for this study within 5-12.5 months.
Interventions
DRUGdexamethasone
dexamethasone 20 mg daily (10 mg BID) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle.
DRUGlenalidomide
15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone
Sponsors
Celgene Corporation
Vaishali Sanchorawala
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: * Histologically confirmed primary systemic (AL) amyloidosis * Tissue amyloid deposits or positive fat aspirate * Meets 1 of the following criteria for AL type disease: * Serum or urine monoclonal protein by immunofixation electrophoresis * Plasmacytosis of bone marrow by monoclonal staining for kappa- or lambda-light chain isotype PATIENT CHARACTERISTICS: Age * 18 and over Performance status * SWOG 0-2 Life expectancy * Not specified Hematopoietic * White blood count\> 3,000/mm\^3 * Hemoglobin \> 8 g/dL * Platelet count \> 100,000/mm\^3 * Absolute neutrophil count \> 1,000/mm\^3 Hepatic * Bilirubin ≤ 2 times upper limit of normal (ULN) * aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 times ULN PRIOR CONCURRENT THERAPY: Biologic therapy * Prior thalidomide for AL amyloidosis allowed Chemotherapy * More than 4 weeks since prior cytotoxic chemotherapy Endocrine therapy * Prior steroids for AL amyloidosis allowed Radiotherapy * More than 4 weeks since prior radiotherapy Surgery * Prior surgery allowed Other * Recovered from all prior therapy
Exclusion criteria
* No secondary or familial amyloidosis * No multiple myeloma, defined as ≥ 30% plasma cells in bone marrow biopsy specimen OR lytic bone lesions * No prior CC-5013 Renal * No dialysis Cardiovascular * No symptomatic cardiac arrhythmia * No oxygen-dependent restrictive cardiomyopathy Other * No untreated or uncontrolled infection * No other malignancy except basal cell skin cancer or carcinoma in situ of the cervix or breast * No other serious medical illness that would preclude study participation * No history of hypersensitivity reaction to thalidomide * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Removed From Study Treatment Due to Toxicities | 1 year | — |
| Number of Patients With Hematologic Response With Single-agent CC-5013 | 3 months | Complete response = Absence of detectable monoclonal protein in serum or urine by immunofixation electrophoresis, less than 5% plasma cells on bone marrow biopsy without clonal dominance of kappa or lambda isotype, and normal serum free light chain assay. Partial response= For patients with detectable and quantifiable monoclonal marrow plasmacytosis= a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. For patients with a detectable monoclonal peak on serum or urine protein electrophoresis= a reduction in the peak height of 50% or more. For patients with quantifiable urinary kappa or lambda chain concentration= a 50% reduction in daily light chain excretion in 24 hour urine. For patients with an elevated serum free light chain assay, a reduction of 50% or more. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Patients Who Received Both CC-5013 and Dexamethasone and Had a Hematologic Response | 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Revlimid lenalidomide 15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone 20 mg daily (10 mg twice daily) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle.
dexamethasone: dexamethasone 20 mg daily (10 mg twice daily) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle.
lenalidomide: 15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone | 82 |
| Total | 82 |
Baseline characteristics
| Characteristic | Revlimid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 24 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants |
| Dialysis y/n Not on dialysis | 75 Participants |
| Dialysis y/n on dialysis | 7 Participants |
| Gender Female | 29 Participants |
| Gender Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 82 / 82 |
| serious Total, serious adverse events | 82 / 82 |
Outcome results
Primary
Number of Patients Removed From Study Treatment Due to Toxicities
Time frame: 1 year
Population: Number of patients who had at least one dose of CC-5013
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Revlimid | Number of Patients Removed From Study Treatment Due to Toxicities | 31 participants |
Primary
Number of Patients With Hematologic Response With Single-agent CC-5013
Complete response = Absence of detectable monoclonal protein in serum or urine by immunofixation electrophoresis, less than 5% plasma cells on bone marrow biopsy without clonal dominance of kappa or lambda isotype, and normal serum free light chain assay. Partial response= For patients with detectable and quantifiable monoclonal marrow plasmacytosis= a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. For patients with a detectable monoclonal peak on serum or urine protein electrophoresis= a reduction in the peak height of 50% or more. For patients with quantifiable urinary kappa or lambda chain concentration= a 50% reduction in daily light chain excretion in 24 hour urine. For patients with an elevated serum free light chain assay, a reduction of 50% or more.
Time frame: 3 months
Population: Participants who received at least 3 cycles of single-agent CC-5013 and underwent subsequent evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Revlimid | Number of Patients With Hematologic Response With Single-agent CC-5013 | 5 Participants |
Secondary
Number of Patients Who Received Both CC-5013 and Dexamethasone and Had a Hematologic Response
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Revlimid | Number of Patients Who Received Both CC-5013 and Dexamethasone and Had a Hematologic Response | 26 participants |