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

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.

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.