CC-5013 With or Without Dexamethasone in Treating Patients With Primary Systemic Amyloidosis

Phase 2

Completed

Conditions: Multiple Myeloma

Interventions: Drug: dexamethasone
Drug: lenalidomide

Registration Number: NCT00091260

Lead Sponsor: Vaishali Sanchorawala

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
revlimid	dexamethasone	lenalidomide 15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone 20 mg daily (10 mg BID) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle.
revlimid	lenalidomide	lenalidomide 15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone 20 mg daily (10 mg BID) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle.

Primary Outcome Measures

Name	Time	Method
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.