Pomalidomide/Cyclophosphamide/Dexamethasone in Relapse Refractory Myeloma: Safety Profile in Mexicans

Study Overview
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Brief Summary
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Despite available therapies, MM uniformly fatal and participants who have received prior lenalidomide (Len) and bortezomib have a median overall survival (OS) of 9 months. Pomalidomide (Pom) plus low-dose dexamethasone (Dex) significantly improved efficacy parameters in terms of progression free survival (PFS), OS, and overall response (ORR) compared with high-dose Dex in participants with refractory or relapsed, and refractory MM, including participants with disease refractory to both bortezomib and lenalidomide. Alkylating agents also represent standard therapies for participants with MM. There are some reports demonstrating combination of Len and continuous cyclophosphamide (Cy) achieve an ORR of 50% in Len refractory participants, suggesting Cy may be able to overcome resistance to Len. The investigators aimed to assess the safety in Mexican MM participants in relapse/refractory stage of the triple combination: IV Cy in combination with Pom plus Dex until disease progression. A multicenter study is proposed. Primary endpoint: Safety. Efficacy as secondary endpoint: PF, OS and ORR.

Detailed Description
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Multiple myeloma is a plasma cell malignancy with accounts for about 1% of all cancers. Despite available therapies, the disease remains uniformly fatal and participants who have received prior lenalidomide and bortezomib have a median overall survival of 9 months. Combination therapy is often used in clinical practice. In an attempt to overcome drug/clone resistance, other report with pomalidomide, dexamethasone and cyclophosphamide (PomCyDex) show efficacy and safety information, regimen for refractory myeloma patients with higher overall response rate than pomalidomide and dexamethasone. In this case a phase II trial scheme is proposed: 1. Pomalidomide at 4 mg orally on days 1-21 of a 28 day cycle, 2. Cyclophosphamide 300 mg IV on days 1 and 15 of a 28 day cycle; and 3. Dexamethasone 40 mg PO weekly. Participants who were >75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone are going to receive 20 mg dexamethasone on the same schedule. Pomalidomide is a drug wide studied in American and European population, but not in México. Even it has been approved by local Regulatory authority, there is not any trial supporting data about safety and efficacy in Mexican population. Alkylating agents are very active in MM, and in combination with novel therapies, such as immunomodulatory drugs, has shown to enhance efficacy in relapsed/refractory setting. It is proposed phase 2 study to assess safety and efficacy of treatment with Pomalidomide in combination with Cyclophosphamide and dexamethasone in a sample of Mexican RRMM participants from ISSSTE.

Official Title
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Multicenter Study of Pomalidomide, Cyclophosphamide, and Dexamethasone in Relapsed Refractory Myeloma: Safety Profile in Mexican Population

Conditions
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Multiple Myeloma in Relapse, Multiple Myeloma Progression, Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Pomalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old Relapsed and refractory multiple myeloma patients that had received ≥2 prior lines of therapies including a proteasome inhibitor and Lenalidomide; if cyclophosphamide was included in a previous line, complete scheme has to be finished at least 6 months previously to initiate in this IIT. Measurable disease as defined by the presence of 1 of the following: serum monoclonal protein ≥0.5 g/dL; urine monoclonal protein >200 mg/24 h; or serum involved free light chain ≥10 mg/dL and abnormal serum free light chain ratio. ECOG 0 to 2 Serum creatinine level <3mg/dL. Absolute neutrophil count ≥1000/mm3, and a platelet count ≥30 000/mm3. Females of childbearing potential has to have a negative serum or urine pregnancy test within 10 to 14 days prior to, and within 24 hours of, starting pomalidomide. A washout period of 2 weeks prior to cycle 1 day 1 from prior therapies are required. Exclusion Criteria: Patients with known hypersensitivity to thalidomide or lenalidomide Patients who had HIV or active hepatitis B or C; Patients with grade 3 or more neuropathy Patients with active malignancy requiring therapy within the next year.

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
Interventional Model Description: Interventional phase 2, multicentric, open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Pomalidomide at 4 mg orally on days 1-21 of a 28 day cycle Cyclophosphamide 300 mg IV on days 1 and 15 of a 28 day cycle. Dexamethasone 40 mg PO weekly.(Or 20 mg if patients are older than 75 years ) | Drug: Pomalidomide<br>* Pomalidomide at 4 mg orally on days 1-21 of a 28 day cycle Cyclophosphamide 300 mg IV on days 1 and 15 of a 28 day cycle. Dexamethasone 40 mg PO weekly.(Or 20 mg if patients are older than 75 years )<br>* Other names: Dexamethasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of Treatment - Emergent Adverse Events | Adverse events leading to death or to discontinuation from treatment, events classified grade 3 or higher, study drug-related events, and serious adverse events are going to be listed separately. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as secondary endpoints: progression free survival, overall survival and overall response rate | For the secondary end point, ORR and its 95% confidence interval are going to be calculated for the study groups using the exact binomial method | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Relapse, Progression, Pomalidomide