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

Phase 3

Completed

Conditions: Multiple Myeloma

Interventions: Drug: lenalidomide
Drug: dexamethasone

Registration Number: NCT00179647

Lead Sponsor: Celgene Corporation

Brief 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1913

Inclusion Criteria

Must understand and voluntarily sign an informed consent form.
Must be > or = to 18 years of age at the time of signing the informed consent form.
Must be able to adhere to the study visit schedule and other protocol requirements.
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.
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.
Measurable levels of myeloma paraprotein in serum (>/=0.5 g/dL) or urine (>/=0.2 g excreted in a 24-hour collection sample).
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
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

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
Pregnant or lactating females.
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.
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)
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.
Known hypersensitivity to thalidomide or dexamethasone.
Prior history of uncontrollable side effects to dexamethasone therapy.
The development of a desquamating rash while taking thalidomide.
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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lenalidomide 5-25 mg, w/wo dexamethasone	dexamethasone	single-arm, open-label, lenalidomide, 5-25 mg, 21/28 days, with/without dexamethasone
Lenalidomide 5-25 mg, w/wo dexamethasone	lenalidomide	single-arm, open-label, lenalidomide, 5-25 mg, 21/28 days, with/without dexamethasone

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events Summarized by System Organ Class, Preferred Term, Severity, Seriousness, and Relationship to Treatment.	Median time-on-study=18.3 weeks	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.
Overall Incidence of Adverse Events	Median time-on-study=18.3 weeks	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (69): University of Texas Southwestern Medical Center
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Dallas, Texas, United States
Mayo Clinic
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Scottsdale, Arizona, United States
Cedar Sinai Medical CenterDept of Medicine
🇺🇸
Los Angeles, California, United States
Emory University
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Atlanta, Georgia, United States
Stanford Cancer Center
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Stanford, California, United States
University of Maryland Medical Center Greenbaum Cancer Ctr
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Baltimore, Maryland, United States
Alta Bates Cancer Center
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Berkeley, California, United States
Scripps Cancer Center
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La Jolla, California, United States
Kaiser Permanente Medical Center
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Vallejo, California, United States
Ochsner Clinic Foundation
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New Orleans, Louisiana, United States
Gulf Coast Oncology
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St. Petersburg, Florida, United States
Yale University School of Medicine
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New Haven, Connecticut, United States
Wichita CCOP
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Wichita, Kansas, United States
The Palm Beach Cancer Institute
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West Palm Beach, Florida, United States
NY Presbyterian Hospital/Weill Medical College-Cornell University
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New York, New York, United States
Deaconess Billings Clinic
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Billings, Montana, United States
New York Medical Center, MBCCOP
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Bronx, New York, United States
Northwestern University Med CtrDivision of Hem/Onc
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Chicago, Illinois, United States
Rush Cancer Institute
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Chicago, Illinois, United States
North Shore Hematology/Oncology Associates, PC
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East Setauket, New York, United States
Siteman Cancer Center
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St. Louis, Missouri, United States
SUNY Upstate Medical University
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Syracuse, New York, United States
Carolinas Hematology-Oncology Associates
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Charlotte, North Carolina, United States
SUNY Health Science Center - Brooklyn
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Brooklyn, New York, United States
Kaiser Permanente Medical Group
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San Diego, California, United States
University of Miami Medical School
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Miami, Florida, United States
Indiana Univ Cancer Center Bone Marrow Transplantation Program Indiana Cancer Research Institute
🇺🇸
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Nevada Cancer Center
🇺🇸
Las Vegas, Nevada, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Huntsman Cancer Institute
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Salt Lake City, Utah, United States
Intermountain Hematology/Oncology
🇺🇸
Salt Lake City, Utah, United States
Swedish Cancer Institute
🇺🇸
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
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Seattle, Washington, United States
University of ColoradoHealth Science Center
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Aurora, Colorado, United States
Rocky Mountain Cancer Center-Midtown
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Denver, Colorado, United States
H Lee Moffitt Cancer Center
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Tampa, Florida, United States
Center for Cancer And Blood Disorders
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Bethesda, Maryland, United States
Mayo Clinic Cancer Center
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Rochester, Minnesota, United States
Methodist Cancer Center
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Omaha, Nebraska, United States
Kaiser Permanente Northwest RegionCenter for Health Research
🇺🇸
Portland, Oregon, United States
Oncology Alliance
🇺🇸
Milwaukee, Wisconsin, United States
Wake Forest University School of Medicine
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Winston-Salem, North Carolina, United States
Hematology Oncology, PC
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Stamford, Connecticut, United States
Mount Sinai Comprehensive Cancer Center
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Miami Beach, Florida, United States
Delaware Clinical & Laboratory Physicians, PA
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Newark, Delaware, United States
Jackson Oncology Associates
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Jackson, Mississippi, United States
Dartmouth Hitchcock Medical Center-Norris Cotton Cancer Center
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Lebanon, New Hampshire, United States
The Cancer Center at Hackensack University Medical Center
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Hackensack, New Jersey, United States
Mid Ohio Oncology & Hematology, Inc.
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Columbus, Ohio, United States
St. Vincent's Comprehensive Cancer Center
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New York, New York, United States
Dakota Cancer Institute
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Fargo, North Dakota, United States
Charleston Hematology/Oncology P.A.
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Charleston, South Carolina, United States
Avera Research Institute
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Sioux Falls, South Dakota, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States
University of Pennsylvania Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Western Pennsylvania Cancer Institute
🇺🇸
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
South Carolina Oncology Assoc
🇺🇸
Columbia, South Carolina, United States
Medical College of Virginis, North Hospital
🇺🇸
Richmond, Virginia, United States
Gunderson Clinic
🇺🇸
LaCrosse, Wisconsin, United States
Marshfield Clinic
🇺🇸
Marshfield, Wisconsin, United States
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
Leukemia/BMT Program of BCDiv of Hem, Vancouver Gen Hosp
🇨🇦
Vancouver, British Columbia, Canada
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
University of Kansas Medical Center
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Kansas City, Kansas, United States