Multiple myeloma and moderate or severe renal impairment a type of bone marrow cancer multiple myeloma
Conditions
Interventions
All subjects will receive oral doses of pomalidomide, at a starting dose of 4
mg on Days 1to 21 of a 28-day cycle and low-dose dexamethasone administered
orally at a starting dose of 40 mg/day in su
Sponsors
Celgene Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria to be enrolled in the study., 1. Must be * 18 years at the time of signing the informed consent form., 2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted., 3. Able to adhere to the study visit schedule and other protocol requirements., 4. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein * 0.5 g/dL or urine M-protein * 200 mg/24 hours)., 5. Subjects must have had at least 1 prior antimyeloma regimen including lenalidomide and documented progression as per the IMWG uniform response criteria (Durie, 2006) during or after the last antimyeloma regimen. Induction therapy followed by ASCT and consolidation/ maintenance will be considered as one regimen., 6. Subjects must have an impaired renal function with an estimated GFR of, < 45 mL/min/1.73 m2 according to the MDRD equation., a. Impaired renal function must be due to multiple myeloma which needs to be, confirmed by kidney biopsy., b. Subjects may have acute myeloma related renal failure or chronic myeloma related renal failure; they may also have been treated with dialysis before, including dialysis with high cut off membranes., 7. ECOG performance status score of 0, 1, or 2, 8. Females of childbearing potential must:, a. Have two negative pregnancy tests as verified by the study doctor prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence from heterosexual contact., b. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy., 9. Male subjects must:, a. Must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following IP discontinuation, even if he has undergone a successful vasectomy.
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a subject from enrollment, 1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study., 2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study., 3. Renal insufficiency due to other reasons than multiple myeloma or due to hypercalcaemia only., 4. Any of the following laboratory abnormalities:, a. Absolute neutrophil count (ANC) < 1,000/*L, b. Subject with platelet count < 50,000/*L are not eligible regardless of the percentage of plasma cells in the bone marrow, c. Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L), d. Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted), e. Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN), f. Serum total bilirubin > 2.0 mg/dL (34.2 *mol/L); or > 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia, 5. Prior history of malignancies, other than MM, unless the subject has been free of the disease for * 5 years; exceptions include the following:, a. Basal or squamous cell carcinoma of the skin, b. Carcinoma in situ of the cervix or breast, c. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b), 6. Previous therapy with pomalidomide., 7. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (this includes * Grade 3 rash during prior thalidomide or lenalidomide therapy)., 8. Peripheral neuropathy * Grade 2., 9. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment and are currently dependent on such treatment., 10. Subjects who are planning for or who are eligible for stem cell transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints: - Overall response rate (ORR) according to the International Myeloma Working Group (IMWG) uniform response criteria with additional clarifications according to the IMWG Consensus panel (Rajkumar, 2011). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: - Assessment of renal response according to the criteria defined by Dimopoulos and Ludwig (Dimopoulos, 2009; Dimopoulos, 2010 b,c; Ludwig, 2010). - Time to Myeloma response, time to renal response, duration of response (DOR), progression-free survival (PFS), time to progression (TTP), overall survival (OS). - Adverse events (AEs) assessment (type, frequency, seriousness, severity, relationship to pomalidomide and/or dexamethasone and outcomes) including second primary malignancy (SPM). - Pharmacokinetics (PK) of pomalidomide in subjects with relapsed or refractory multiple myeloma and impaired renal function (moderate to severe renal impairment). | — |
Countries
Netherlands
Outcome results
None listed