Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, MM, Revlimid, CC5013, celgene, cc-5013, relapsed/refractory, lenalidomide, dexamethasone, Decadron
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.
Interventions
DRUGlenalidomide
Lenalidomide, 5 mg to 25 mg, QD, orally, for 21 days every 28 days, with or without dexamethasone
DRUGdexamethasone
Dexamethasone, 20 mg to 40 mg, QD, orally, administered under a variety of dosing regimens
Sponsors
Prologue Research International
Celgene Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide 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. | 1,913 |
| Total | 1,913 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 294 |
| Overall Study | Death | 94 |
| Overall Study | Lack of Efficacy | 478 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Other | 960 |
| Overall Study | Withdrawal by Subject | 83 |
Baseline characteristics
| Characteristic | Lenalidomide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 823 Participants |
| Age, Categorical Between 18 and 65 years | 1090 Participants |
| Age Continuous | 63.4 years STANDARD_DEVIATION 10.31 |
| Region of Enrollment Canada | 730 participants |
| Region of Enrollment United States | 1183 participants |
| Sex: Female, Male Female | 762 Participants |
| Sex: Female, Male Male | 1151 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1,877 / 1,913 |
| serious Total, serious adverse events | 878 / 1,913 |
Outcome results
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.
Time frame: Median time-on-study=18.3 weeks
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.
Time frame: Median time-on-study=18.3 weeks
Population: Subjects who received study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide | Overall Incidence of Adverse Events | 1877 Participants |