Expanded Access Program:Lenalidomide With or Without Dexamethasone In Previously Treated Subjects With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Multicenter, Single-Arm, Open-Label, Expanded Access Program for Lenalidomide With or Without Dexamethasone in Previously Treated Subjects With Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00179647
• Other study ID #: CC-5013-MM-016
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: March 10, 2010
• Start date: September 2005
• Est. completion date: April 2009

Study information

• Verified date: March 2010
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Subjects who qualify for participation will receive lenalidomide with or without dexamethasone in 4 week cycles until disease progression is documented or lenalidomide becomes commercially available for the indication of multiple myeloma.

Description:

This was a multicenter, non-randomized, open-label, uncontrolled, single-arm treatment study of lenalidomide as monotherapy or in combination with dexamethasone in subjects with previously treated relapsed or refractory multiple myeloma, with measurable myeloma paraprotein in serum and/or urine. Subjects who met all of the eligibility criteria were enrolled into the study. Screening procedures took place within 28 days of first dose. Subjects who qualified for participation received oral lenalidomide at a dose of 25 mg daily for 21 days every 28 days.

Subjects had the following options for dexamethasone treatment at the discretion of the treating physician:

Option A: No dexamethasone.

Option B: Oral pulse dexamethasone administered at a dose of 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle.

Option C: Oral pulse dexamethasone administered at a dose of 20 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle.

Option D: Oral dexamethasone administered at a dose of 40 mg weekly on Days 1, 8, 15, and 22 for each 28-day cycle for all cycles. Treatment was to be continued as tolerated until disease progression developed.

Doses of lenalidomide were allowed to be reduced first from 25 mg to 15 mg and then in 5-mg decrements due to lenalidomide toxicity. Subjects who could not tolerate a daily dose of 5 mg for 21 days every 28 days were discontinued from treatment. At the discretion of the investigator, doses of dexamethasone were modified due to dexamethasone toxicity. Dose reduction and discontinuation schemes for dexamethasone varied according to the treatment option administered.

Study visits occurred every 2 weeks for the first 3 cycles of therapy and then every 4 weeks after the third cycle until disease progression was documented, study drug was discontinued for another reason, or lenalidomide became commercially available for this indication.

Other known NCT identifiers

• NCT00331903

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1913
• Est. completion date: April 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Must understand and voluntarily sign an informed consent form.

2. Must be > or = to 18 years of age at the time of signing the informed consent form.

3. Must be able to adhere to the study visit schedule and other protocol requirements.

4. Must be diagnosed with multiple myeloma that is progressing after at least 2 cycles of anti-myeloma treatment or that has relapsed with progressive disease after treatment.

5. Subjects may have been previously treated with thalidomide and/or radiation therapy. In addition, radiation therapy initiated prior to or at baseline (Day 1) may be given concurrently with study therapy, provided that all other eligibility criteria are satisfied.

6. Measurable levels of myeloma paraprotein in serum (>/=0.5 g/dL) or urine (>/=0.2 g excreted in a 24-hour collection sample).

7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.

8. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study medication.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

2. Pregnant or lactating females.

3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

4. Any of the following laboratory abnormalities:

1. Absolute neutrophil count (ANC) <1,000 cells/mm3 (1.0 x 109/L)

2. Platelet count <75,000/mm3 (75 x 109/L) for subjects in whom <50% of the bone marrow nucleated cells are plasma cells.

3. Platelet count <30,000/mm3 (30x109/L) for subjects in whom >/= 50% of bone marrow nucleated cells are plasma cells.

4. Serum creatinine >2.5 mg/dL (221 mmol/L)

5. Serum glutamic oxaloacetic transaminase (SGOT, aspartate transaminase [AST]) or serum glutamic pyruvic transaminase (SGPT, alanine transaminase [ALT]) >3.0 x upper limit of normal (ULN)

6. Serum total bilirubin >2.0 mg/dL (34 mmol/L)

5. Prior history of malignancies other than multiple myeloma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for >/= 1 year.

6. Known hypersensitivity to thalidomide or dexamethasone.

7. Prior history of uncontrollable side effects to dexamethasone therapy.

8. The development of a desquamating rash while taking thalidomide.

9. Use of any standard/experimental anti-myeloma drug therapy within 28 days of the initiation of study drug treatment or use of any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of the initiation of study drug treatment.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• lenalidomide
Lenalidomide, 5 mg to 25 mg, QD, orally, for 21 days every 28 days, with or without dexamethasone
• dexamethasone
Dexamethasone, 20 mg to 40 mg, QD, orally, administered under a variety of dosing regimens

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Dalhousie University Queen Elizabeth II Health Services Centre	Halifax	Nova Scotia
Canada	McGill University	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Leukemia/BMT Program of BCDiv of Hem, Vancouver Gen Hosp	Vancouver	British Columbia
United States	Emory University	Atlanta	Georgia
United States	University of ColoradoHealth Science Center	Aurora	Colorado
United States	University of Maryland Medical Center Greenbaum Cancer Ctr	Baltimore	Maryland
United States	Alta Bates Cancer Center	Berkeley	California
United States	Center for Cancer And Blood Disorders	Bethesda	Maryland
United States	Deaconess Billings Clinic	Billings	Montana
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	New York Medical Center, MBCCOP	Bronx	New York
United States	SUNY Health Science Center - Brooklyn	Brooklyn	New York
United States	Charleston Hematology/Oncology P.A.	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Hematology-Oncology Associates	Charlotte	North Carolina
United States	Northwestern University Med CtrDivision of Hem/Onc	Chicago	Illinois
United States	Rush Cancer Institute	Chicago	Illinois
United States	South Carolina Oncology Assoc	Columbia	South Carolina
United States	Mid Ohio Oncology & Hematology, Inc.	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Rocky Mountain Cancer Center-Midtown	Denver	Colorado
United States	North Shore Hematology/Oncology Associates, PC	East Setauket	New York
United States	Dakota Cancer Institute	Fargo	North Dakota
United States	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Indiana Univ Cancer Center Bone Marrow Transplantation Program Indiana Cancer Research Institute	Indianapolis	Indiana
United States	Jackson Oncology Associates	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Cancer Center	La Jolla	California
United States	Gunderson Clinic	LaCrosse	Wisconsin
United States	Nevada Cancer Center	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center-Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Cedar Sinai Medical CenterDept of Medicine	Los Angeles	California
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	University of Miami Medical School	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Oncology Alliance	Milwaukee	Wisconsin
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	NY Presbyterian Hospital/Weill Medical College-Cornell University	New York	New York
United States	St. Vincent's Comprehensive Cancer Center	New York	New York
United States	Delaware Clinical & Laboratory Physicians, PA	Newark	Delaware
United States	Methodist Cancer Center	Omaha	Nebraska
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Northwest RegionCenter for Health Research	Portland	Oregon
United States	Medical College of Virginis, North Hospital	Richmond	Virginia
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Intermountain Hematology/Oncology	Salt Lake City	Utah
United States	Kaiser Permanente Medical Group	San Diego	California
United States	Mayo Clinic	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Avera Research Institute	Sioux Falls	South Dakota
United States	Siteman Cancer Center	St. Louis	Missouri
United States	Gulf Coast Oncology	St. Petersburg	Florida
United States	Hematology Oncology, PC	Stamford	Connecticut
United States	Stanford Cancer Center	Stanford	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	H Lee Moffitt Cancer Center	Tampa	Florida
United States	Kaiser Permanente Medical Center	Vallejo	California
United States	The Palm Beach Cancer Institute	West Palm Beach	Florida
United States	Wichita CCOP	Wichita	Kansas
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Celgene Corporation	Prologue Research International

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events Summarized by System Organ Class, Preferred Term, Severity, Seriousness, and Relationship to Treatment.	Data from all subjects who received any study drug were included in the analysis. Adverse events were classified using the Medical Dictionary for Regulatory Activities (MedDRA) classification system. A subject having the same event more than once was counted only once. Adverse events were summarized by worst NCI (National Cancer Institute) CTCAE (Common Terminology Criteria for Adverse Events) VERSION 3.0 grade. Incidence was defined as the number of subjects who experienced an adverse event within their period of participation in this study.	Median time-on-study=18.3 weeks	Yes
Primary	Overall Incidence of Adverse Events	Data from all subjects who received any study drug were included in the analysis. Adverse events were classified using the Medical Dictionary for Regulatory Activities (MedDRA) classification system. A subject having the same event more than once was counted only once. Adverse events were summarized by worst NCI (National Cancer Institute) CTCAE (Common Terminology Criteria for Adverse Events) VERSION 3.0 grade. Incidence was defined as the number of subjects who experienced an adverse event within their period of participation in this study.	Median time-on-study=18.3 weeks	Yes