Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis
RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop plasma cells from growing. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may be an effective treatment for primary systemic amyloidosis.
PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with primary systemic amyloidosis.
Multiple Myeloma and Plasma Cell Neoplasm
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Lenalidomide (Revlimid®), Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis|
- Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) [ Time Frame: Duration on study (up to 3 years) ] [ Designated as safety issue: No ]
Response that was confirmed on 2 consecutive evaluations during treatment.
Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.
Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <=100 mg per 24 hours.
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.
- Number of Patients With Organ Response [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: No ]
Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid.
Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%.
- Number of Participants With Severe Adverse Events [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: Yes ]Severe adverse events were defined as grade 3 or higher, at least possibly related to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
- Progression Free Survival (PFS) [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: No ]Progression free survival (PFS) was defined as the time from registration to hematologic progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.
- Overall Survival (OS) [ Time Frame: Duration of study (up to 3 years) ] [ Designated as safety issue: No ]Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
|Study Start Date:||December 2007|
|Study Completion Date:||June 2012|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
Lenalidomide 15mg daily (days 1-21)
Cyclophosphamide 300 mg/m^2 (days 1, 8, 15)
Dexamethasone 40 mg weekly
300 mg/m^2 days 1, 8 & 15 of a 28 day cycle taken orally with foodDrug: dexamethasone
40 mg weekly taken orallyDrug: lenalidomide
15 mg daily days 1-21 of a 28 day cycle taken orally with food
* Assess the hematologic response rate in patients with primary systemic amyloidosis treated with lenalidomide, cyclophosphamide, and dexamethasone.
- Determine the organ response rate in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the time to progression in patients treated with this regimen.
- Determine the survival of 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive cyclophosphamide for up to 1 year. After completion of study treatment, patients are followed every 6 months for up to 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00564889
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Shaji K. Kumar, MD||Mayo Clinic|
|Principal Investigator:||Craig B. Reeder, MD||Mayo Clinic in Arizona|
|Principal Investigator:||Vivek Roy, MD, FACP||Mayo Clinic in Florida|