Multiple Myeloma
Conditions
Keywords
primary systemic amyloidosis
Brief summary
RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of abnormal plasma cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop the abnormal plasma cells from growing. Giving melphalan together with lenalidomide and dexamethasone may be an effective treatment for primary systemic amyloidosis. PURPOSE: This phase II trial is studying the side effects and how well giving melphalan together with lenalidomide and dexamethasone works in treating patients with primary systemic amyloidosis.
Detailed description
OBJECTIVES: Primary * To determine the tolerability and safety of melphalan, lenalidomide, and dexamethasone, in terms of toxicity, in patients with primary systemic amyloidosis. * To determine the hematologic response rate in patients treated with this regimen. Secondary * To assess organ response in patients treated with this regimen. OUTLINE: Patients receive oral lenalidomide once daily on days 1-21, oral melphalan once daily on days 1-4, and oral dexamethasone once on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months until disease progression and then annually thereafter.
Interventions
DRUGdexamethasone
40 mg once weekly
DRUGlenalidomide
10 mg/day D1-21
DRUGmelphalan
5 mg/m2 D1-4
Sponsors
Boston Medical 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
DISEASE CHARACTERISTICS: * Diagnosis of primary systemic amyloidosis PATIENT CHARACTERISTICS: * Not pregnant * Negative pregnancy test * Able to tolerate an anticoagulation regimen (e.g., 325 mg of aspirin per day, therapeutic warfarin, or low molecular weight heparin) PRIOR CONCURRENT THERAPY: * Recovered from prior therapy * Permanent or stable side effects/changes allowed * Prior chemotherapy, thalidomide, lenalidomide, or steroids for amyloidosis allowed * More than 4 weeks since prior and no other concurrent cytotoxic chemotherapy or radiotherapy
Exclusion criteria
* No secondary or familial amyloidosis * No multiple myeloma (≥ 30% plasma cells in bone marrow biopsy or lytic bone lesions) * No prior cumulative doses of oral melphalan \> 200 mg * No more than one prior course of high-dose melphalan with stem cell transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hematologic Response | one year | Complete hematologic response: Absence of detectable monoclonal protein in serum or urine by immunofixation electrophoresis, bone marrow biopsy with less than 5% plasma cells without clonal dominance of kappa or lambda isotype, and normal serum free light chain assay. Partial hematologic response: Amyloid patients have highly individualized measures of disease burden. 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 (concentration x 24 hour urine volume). For patients with an elevated serum free light chain assay, reduction of 50% or more. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Organs Improved or Stable Based on Description Below: | one year | Renal response - \> 50% decrease in daily 24 hour proteinuria, without worsening renal insufficiency. Hepatic response - decrease of 2 centimeters or more of the liver span and/or decrease of the alkaline phosphatase by 50% if elevated at baseline. Cardiac response - decrease of 2 millimeters or more in mean left ventricular wall thickness in patients with baseline wall thickness \> 11 mm or a decrease in New York Heart Association heart failure class. Autonomic nervous system response - resolution of orthostatic vital signs and symptoms, and resolution of symptoms of gastric atony or of functional ileus. Gastrointestinal response - a greater than one grade improvement in diarrhea due to biopsy proven amyloid. Peripheral nervous system response - resolution of clinical signs of peripheral neuropathy. |
| Number of Participants Removed From Study Due to Toxicities | One year | Number of study participants removed from study treatment due to toxicities |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Melphalan Revlimid and Dexamethasone Melphalan Lenalidomide Dexamethasone
dexamethasone: 40 mg once weekly
lenalidomide: 10 mg/day Days 1-21
melphalan: 5 mg/m2 Days 1-4 | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | inability to swallow oral drugs | 1 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Melphalan Revlimid and Dexamethasone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Gender Female | 10 Participants |
| Gender Male | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 16 / 16 |
Outcome results
Primary
Number of Participants With Hematologic Response
Complete hematologic response: Absence of detectable monoclonal protein in serum or urine by immunofixation electrophoresis, bone marrow biopsy with less than 5% plasma cells without clonal dominance of kappa or lambda isotype, and normal serum free light chain assay. Partial hematologic response: Amyloid patients have highly individualized measures of disease burden. 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 (concentration x 24 hour urine volume). For patients with an elevated serum free light chain assay, reduction of 50% or more.
Time frame: one year
Population: Participants who completed at least 3 cycles of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan Revlimid and Dexamethasone | Number of Participants With Hematologic Response | 7 participants |
Secondary
Number of Organs Improved or Stable Based on Description Below:
Renal response - \> 50% decrease in daily 24 hour proteinuria, without worsening renal insufficiency. Hepatic response - decrease of 2 centimeters or more of the liver span and/or decrease of the alkaline phosphatase by 50% if elevated at baseline. Cardiac response - decrease of 2 millimeters or more in mean left ventricular wall thickness in patients with baseline wall thickness \> 11 mm or a decrease in New York Heart Association heart failure class. Autonomic nervous system response - resolution of orthostatic vital signs and symptoms, and resolution of symptoms of gastric atony or of functional ileus. Gastrointestinal response - a greater than one grade improvement in diarrhea due to biopsy proven amyloid. Peripheral nervous system response - resolution of clinical signs of peripheral neuropathy.
Time frame: one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan Revlimid and Dexamethasone | Number of Organs Improved or Stable Based on Description Below: | 10 number of organs stable or improved |
Secondary
Number of Participants Removed From Study Due to Toxicities
Number of study participants removed from study treatment due to toxicities
Time frame: One year
Population: All patients who have had at least one dose of drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Melphalan Revlimid and Dexamethasone | Number of Participants Removed From Study Due to Toxicities | 6 Participants |