Efficacy and Safety of Pomalidomide and Dexamethasone in RRMM Patients With Renal Insufficiency

Study Overview
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Brief Summary
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The primary purpose of the study is to determine the safety and efficacy and to generate PK and biomarker data for the combination of Pomalidomide and low-dose Dexamethasone in patients with relapsed or refractory multiple myeloma, with moderate or severe renal impairment.

Detailed Description
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The study will consist of a Screening phase within 28 days prior to cycle 1 day 1. Subjects once enrolled will enter the Treatment phase, in which patients will be treated until progression, or study discontinuation due to other reasons. Subjects will enter the long term Follow-up phase of the study where data will be collected every 3 months for up to 5 years on Secondary primary malignancies, survival, subsequent anti myeloma treatments and date of progression. Subjects will be recruited into one of 3 cohorts depending on the severity of their renal impairment.

Official Title
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A Phase 2 Multicenter, Open-label Study to Determine the Efficacy and Safety of Pomalidomide (CC-4047) in Combination With Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma and Moderate or Severe Renal Impairment Including Subjects Undergoing Hemodialysis

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Pomalidomide and Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subjects must satisfy the following criteria to be enrolled in the study. 1. 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 International Myeloma Working Group uniform response criteria (Durie, 2006) during or after the last antimyeloma regimen. Induction therapy followed by Autologous Stem Cell Transplant and consolidation/ maintenance will be considered as one regimen. 6. Subjects must have an impaired renal function with an estimated Glomerular Filtrate Rate of < 45 mL/min/1.73 m2 according to the modification of diet in renal disease equation. Impaired renal function must be due to multiple myeloma which needs to be confirmed by kidney biopsy. 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. Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. Renal insufficiency due to other reasons than multiple myeloma or due to hypocalcaemia only. Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years; exceptions include the following: Basal or squamous cell carcinoma of the skin Carcinoma in situ of the cervix or breast Incidental histological finding of prostate cancer (Tumour lymphNode Metastasis 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). 10. Subjects who are planning for or who are eligible for stem cell transplant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomalidomide and low dose Dexamethasone<br>Pomalidomide 4mg, and low dose Dexamethasone, starting at 40mgs(≤ 75 years old) or 20 mg/day (> 75 years old) | Drug: Pomalidomide and Dexamethasone<br> <br> * Other names: Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate efficacy of the combination of pomalidomide and low-dose dexamethasone in subjects with RRMM and impaired renal function | Overall response rate determined by Myeloma responses determined by modified IMWG criteria | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of renal response according to the criteria defined by Dimopoulos and Ludwig (Dimopoulos, 2009; Dimopoulos, 2010 b,c; Ludwig, 2010). | Assessment of renal response according to the criteria defined by Ludwig and Dimopoulos | Approximately 2 years | 
| Time to Myeloma response | Evaluated according to the CTCAE grading | Approximately 2 years | 
| Time to renal response | Evaluated according to the CTCAE grading | Approximately 2 years | 
| Duration of response | Evaluated according to the CTCAE grading | Approximately 2 years | 
| Progression-free survival | Evaluated according to the CTCAE grading | Approximately 2 years | 
| Time to progression | Evaluated according to the CTCAE grading | Approximately 2 years | 
| Overall Survival | Evaluated according to the CTCAE grading | Approximately 2 years | 
| 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 RRMM and impaired renal function (moderate to severe renal impairment). | Approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Relapsed Multiple Myeloma, Refactory Multiple Myeloma, Renal Insufficiency, Pomalidomide, Dexamethasone