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

Vaishali Sanchorawala

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: dexamethasone; Drug: lenalidomide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00091260

CDR0000385687

BUMC-H-23235 (Other Identifier)

CELGENE-RV-AMYL-PI-003 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 82 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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82 participants in 1 patient group

revlimid

Experimental group

Description:

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.

Treatment:

Drug: lenalidomide

Drug: dexamethasone