A Phase 1 Multi-Center, Open-Label, Dose-Escalation Study to Determine the Pharmacokinetics and Safety of Pomalidomide When Given in Combination With Low Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma and Impaired Renal Function
Overview
- Phase
- Phase 1
- Intervention
- 4 mg Oral POM + 40 mg Oral DEX
- Conditions
- Multiple Myeloma
- Sponsor
- Celgene
- Enrollment
- 25
- Locations
- 9
- Primary Endpoint
- PK-Renal clearance (CLr)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to determine the pharmacokinetics (PK) and safety for the combination of pomalidomide (POM) + low-dose dexamethasone (LD- DEX) in subjects with relapsed or refractory Multiple Myeloma (RRMM) and impaired renal function.
Detailed Description
The primary objective of the study is to determine the PK and safety for the combination of POM + (LD-DEX) in subjects with RRMM and impaired renal function. The secondary objective of the study is to evaluate the efficacy of POM + (LD_DEX) in subjects with RRMM and impaired renal function. This is a 3+3 dose escalation design, with one cohort each for patients with severely impaired renal function patients (CrCl \< 30 mL/min) requiring and not requiring dialysis respectively. There will also be one control cohort with normal renal function, these patients will receive 4 mg POM. Dosing will be 21 days out of a 28 day cycle.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must satisfy the following criteria to be enrolled in the study:
- •Must be ≥ 18 years at the time of signing the informed consent form
- •Must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures
- •Must be able to adhere to the study visit schedule and other protocol requirements
- •Must have documented diagnosis of relapsed or refractory multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours)
- •Must have had at least 1 prior anti-myeloma regimen
- •Must have documented progression as per the International Myeloma Working Group uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- •Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation, and must agree to regular pregnancy testing during this timeframe
- •Females must agree to abstain from breastfeeding during study participation and for 28 following discontinuation from study treatment
Exclusion Criteria
- •The presence of any of the following will exclude a subject from enrollment:
- •Peripheral neuropathy ≥ Grade 2
- •Non-secretory multiple myeloma
- •Any of the following laboratory abnormalities:
- •Absolute neutrophil count (ANC) \< 1,000/µL
- •Platelet count \< 75,000/µL
- •Corrected serum calcium \> 14 mg/dL (\> 3.5 mmol/L)
- •Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
- •Serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) or serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) \> 3.0 x upper limit of normal (ULN)
- •Serum total bilirubin \> 2.0 mg/dL
Arms & Interventions
4 mg Oral POM + 40 mg Oral DEX
Oral POM at 4 mg on days 1-21 of a 28-day cycle, Oral DEX at 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on days 1, 8, 15 and 22 of a 28-day cycle
Intervention: 4 mg Oral POM + 40 mg Oral DEX
2 mg Oral POM + 40 mg Oral DEX
Oral POM at 2 mg on days 1-21 of a 28-day cycle, Oral DEX at 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on days 1, 8, 15 and 22 of a 28-day cycle
Intervention: 2 mg Oral POM + 40 mg Oral DEX
Outcomes
Primary Outcomes
PK-Renal clearance (CLr)
Time Frame: 24 times over 7 months
PK-Renal clearance (CLr)
PK-Effective terminal half-life (T1/2)
Time Frame: 24 times over 7 months
PK-Effective terminal half-life (T1/2)
PK-Area under the plasma concentration time curve (AUC)
Time Frame: Up to 24 times over 7 months
PK-Area under the plasma concentration time curve (AUC)
PK-Apparent total body clearance (CL/F)
Time Frame: 24 times up to 7 months
PK-Apparent total body clearance (CL/F)
PK-Time to maximum plasma concentration (Cmax)
Time Frame: 24 times over 7 months
PK-Time to maximum plasma concentration (Cmax)
PK-Apparent volume of distribution (V/F)
Time Frame: 24 times over 7 months
PK-Apparent volume of distribution (V/F)
Secondary Outcomes
- Duration of response(Up to 5 years)
- Number of participants alive(Up to 5 years)
- Number of participants with adverse events (AEs)(Up to 5 years)
- Time to response(Up to 5 years)