Evaluation of Safety of Pomalidomide in Combination With Dexamethasone (Low Dose) in Patients With Refractory or Relapsed and Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the safety and efficacy and to generate PK and biomarker data for the combination of pomalidomide and low-dose dexamethasone in patients with refractory or relapsed and refractory multiple myeloma. The study consists of a Screening phase within 28 days prior to cycle 1 day 1, a Treatment phase and a Follow-up phase which starts within 28 days of discontinuation from study treatment, every 3 months for up to 5 years. In addition, the collection of steady-state PK data from a large population will enable robust population PK and assess Pomalidomide exposure response analyses. The exploratory objectives of the study are to investigate potential markers predictive of POM response or resistance and pharmacodynamic markers.

Official Title
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A Multicenter, Single-arm, Open-label Study With Pomalidomide in Combination With Low Dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Pomalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years old, who must understand and voluntarily sign an Informed Consent. Patients must have documented diagnosis of Multiple Myeloma and have measurable disease. Patients must have undergone prior treatment with ≥ 2 treatments lines, of anti-myeloma therapy. Patients must have either refractory or relapsed and refractory disease. Patients must have received at least 2 consecutive cycles of prior treatment that include lenalidomide and bortezomib, either alone or in combination regimens. Patients must have received adequate alkylator therapy Exclusion Criteria: Prior history of malignancies, other than Multiple Myeloma. Previous therapy with Pomalidomide, hypersensitivity to thalidomide and lenalidomide or dexamethasone. Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant. Patients who are planning for or who are eligible for stem cell transplant. Patients who received major surgery and any anti-myeloma drug therapy within the last 14 days of starting study treatment. Patients with a current disease that can interfere with protocol procedures or study treatment. Patients unable or unwilling to undergo antithrombotic prophylactic treatment. Pregnant or breastfeeding females.

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 plus Dexamethasone<br>Pomalidomide 4mg by mouth (PO) daily days 1 through 21 of a 28 day cycle and dexamethasone 40mg/day PO for those ≤75 years of age or 20mg/day for those greater than 75 years of age on Days 1, 8, 15 and 22 of a 28 day cycle. | Drug: Pomalidomide<br>* Oral Pomalidomide at the starting dose of 4 mg on Days 1-21 of a 28-day cycle<br>Drug: Dexamethasone<br>* Oral Low dose Dexamethasone at the starting dose of 40mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, regardless of etiology. Any worsening (i.e., any significant adverse change in the frequency or intensity of a pre- existing condition) was considered an AE. The severity of AEs were graded based on the symptoms according to version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs. A SAE = AE occurring at any dose that: Results in death; Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect | From the first dose of study treatment up to 28 days following the last dose of study treatment. The median duration of treatment with pomalidomide and LD-dex was 21.4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response | Overall response rate (ORR) was defined as the percentage of participants with a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) according to the International Myeloma Working Group uniform response criteria (IMWG URC) assessed by the Investigator. Responses must have been confirmed at at least 2 consecutive assessments before the institution of any new therapy with no known evidence of progressive or new bone lesions | Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks | 
| Time to Response | Time to response was defined as the time from treatment enrollment to the first documentation of response (sCR, CR, VGPR or PR) based on IMWG criteria. | Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks | 
| Kaplan Meier Estimate of Duration of Response | Duration of response, calculated for responders only, was defined as time from the initial documented response (SCR, CR, VGPR or PR) to the first confirmed disease progression, or death if no disease progression was recorded. Participants without a documented progression were censored at the time of their last tumor assessment. | From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months | 
| Kaplan Meier Estimate of Progression Free Survival (PFS) According to the European Medicines Agency Guidelines | Progression free survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until either PD or death (any cause). Participants without an event (either a documented PD or death) at the time of study end were censored at the time of their last documented disease assessment or at the IVRS enrollment date if no disease assessment was conducted. | From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months | 
| Kaplan Meier Estimate of Time to Progression | Time to progression was calculated as the time from study enrollment until first recorded disease progression as determined by the site investigator based on the IMWG criteria, or until death due to progression. Participants not experiencing a documented progression were censored at the time of their last tumor assessment (or at the time of trial enrollment if no assessment was conducted). | From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months | 
| Kaplan Meier Estimate of Overall Survival (OS) | Overall survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until death due to any cause. Participants who did not have death data at the time of study end/analysis were censored at the time they were last known to be alive. | From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months | 
| Pomalidomide Exposure - Apparent (Oral) Clearance (CL/F) | Pharmacokinetic (PK) parameters are derived from pomalidomide concentration versus time data. | Cycles 1, 2, 3, 4, 5, 6 | 
| Pomalidomide Exposure - Apparent Volume of Distribution (V/F) | Pharmacokinetic (PK) parameters are derived from Pomalidomide concentration versus time data. | Cycles 1, 2, 3, 4, 5, 6 | 
| Cytogenetic Analysis | Cytogenetic analysis was to be performed using fluorescence in situ hybridization (FISH) methodology at a local laboratory, to evaluate the relationship between cytogenetic profiles and the combination of POM and LD-DEX in terms of response and outcome. | Study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Relapsed Multiple Myeloma, Relapsed and refractory Multiple Myeloma, Pomalidomide, Dexamethasone