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

• ClinicalTrials.gov Identifier: NCT00091260
• Recruitment Status: Completed
• First Posted: September 9, 2004
• Results First Posted: February 20, 2017
• Last Update Posted: February 20, 2017
• Sponsor: Vaishali Sanchorawala
• Collaborator: Celgene Corporation
• Information provided by (Responsible Party): Vaishali Sanchorawala, Boston Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: dexamethasone; Drug: lenalidomide	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of the Immunomodulatory Drug CC-5013 for Patients With AL Amyloidosis
• Study Start Date: January 2004
• Actual Primary Completion Date: July 2012
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: revlimid; 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.	Drug: dexamethasone; dexamethasone 20 mg daily (10 mg BID) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle.; Other Name: dexamethasone acetate; Drug: lenalidomide; 15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone; Other Name: revlimid; CC-5013

Outcome Measures

Primary Outcome Measures :

1. Number of Patients Removed From Study Treatment Due to Toxicities [ Time Frame: 1 year ]
2. Number of Patients With Hematologic Response With Single-agent CC-5013 [ Time Frame: 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 Outcome Measures :

1. Number of Patients Who Received Both CC-5013 and Dexamethasone and Had a Hematologic Response [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Cancer Research Center at Boston Medical Center

Boston, Massachusetts, United States, 02118

Sponsors and Collaborators

Vaishali Sanchorawala

Celgene Corporation

Investigators

• Principal Investigator: David C. Seldin, MD, PhD; Boston Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lichtman EI, Seldin DC, Shelton A, Sanchorawala V. Single agent lenalidomide three times a week induces hematologic responses in AL amyloidosis patients on dialysis. Am J Hematol. 2014 Jul;89(7):706-8. doi: 10.1002/ajh.23722. Epub 2014 Apr 10.

• Responsible Party: Vaishali Sanchorawala, Principal Investigator, Boston Medical Center
• ClinicalTrials.gov Identifier: NCT00091260
• Other Study ID Numbers: CDR0000385687; BUMC-H-23235 ( Other Identifier: Boston University Medical Center IRB ); CELGENE-RV-AMYL-PI-003 ( Other Grant/Funding Number: Celgene )
• First Posted: September 9, 2004
• Results First Posted: February 20, 2017
• Last Update Posted: February 20, 2017
• Last Verified: December 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Vaishali Sanchorawala, Boston Medical Center:

primary systemic amyloidosis

Additional relevant MeSH terms:

Multiple Myeloma; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Dexamethasone; Dexamethasone acetate; Lenalidomide; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones