Clinical trial NCT00179647: Expanded Access Program:Lenalidomide With or Without Dexamethasone In Previously Treated Subjects With Multiple Myeloma
Official title: A Multicenter, Single-Arm, Open-Label, Expanded Access Program for Lenalidomide With or Without Dexamethasone in Previously Treated Subjects With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
MM
Revlimid
CC5013
celgene
cc-5013
relapsed/refractory
lenalidomide
dexamethasone
Decadron
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: Prologue Research International
First posted: 2005-09-16
Enrollment: 1913
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Adverse Events Summarized by System Organ Class, Preferred Term, Severity, Seriousness, and Relationship to Treatment.
timeFrame: Median time-on-study=18.3 weeks
measure: Overall Incidence of Adverse Events
timeFrame: Median time-on-study=18.3 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Cancer Center
state: California
city: La Jolla
country: United States
facility: Scripps Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedar Sinai Medical CenterDept of Medicine
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Aurora
country: United States
facility: University of ColoradoHealth Science Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Midtown
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Stamford
country: United States
facility: Hematology Oncology, PC
state: Connecticut
city: Newark
country: United States
facility: Delaware Clinical & Laboratory Physicians, PA
state: Delaware
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami Medical School
state: Florida
city: St. Petersburg
country: United States
facility: Gulf Coast Oncology
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: West Palm Beach
country: United States
facility: The Palm Beach Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Med CtrDivision of Hem/Onc
state: Illinois
city: Chicago
country: United States
facility: Rush Cancer Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Cancer Center Bone Marrow Transplantation Program Indiana Cancer Research Institute
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center Greenbaum Cancer Ctr
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer And Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: Jackson Oncology Associates
state: Mississippi
city: St. Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Billings
country: United States
facility: Deaconess Billings Clinic
state: Montana
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center-Norris Cotton Cancer Center
state: New Hampshire
city: Hackensack
country: United States
facility: The Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: New York Medical Center, MBCCOP
state: New York
city: Brooklyn
country: United States
facility: SUNY Health Science Center - Brooklyn
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology/Oncology Associates, PC
state: New York
city: New York
country: United States
facility: St. Vincent's Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: NY Presbyterian Hospital/Weill Medical College-Cornell University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Hematology-Oncology Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Fargo
country: United States
facility: Dakota Cancer Institute
state: North Dakota
city: Columbus
country: United States
facility: Mid Ohio Oncology & Hematology, Inc.
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente Northwest RegionCenter for Health Research
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology/Oncology P.A.
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: South Carolina Oncology Assoc
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Research Institute
state: South Dakota
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: Intermountain Hematology/Oncology
state: Utah
city: Richmond
country: United States
facility: Medical College of Virginis, North Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: LaCrosse
country: United States
facility: Gunderson Clinic
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Oncology Alliance
state: Wisconsin
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: Leukemia/BMT Program of BCDiv of Hem, Vancouver Gen Hosp
state: British Columbia
city: Halifax
country: Canada
facility: Dalhousie University Queen Elizabeth II Health Services Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Celgene Corporation
name: Robert Knight, MD
role: STUDY_DIRECTOR
References:
citation: Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE, Mansoor A, Chen C, Masih-Khan E, Trieu Y, Bruyere H, Stewart DA, Bahlis NJ. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood. 2009 Jul 16;114(3):522-5. doi: 10.1182/blood-2008-12-193458. Epub 2009 Mar 30.