A Companion Study for Studies THAL-MM-003, CC-5013-MM-009, and CC-5013-MM-010 for Subjects With Multiple Myeloma

Study Overview
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Brief Summary
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The study evaluated the safety of Lenalidomide monotherapy in participants with advanced multiple myeloma who had discontinued treatment with combination thalidomide plus high-dose dexamethasone or high-dose dexamethasone alone in studies Thal-MM-003, CC-5013-MM-009 and CC-5013-MM-010 due to the development of documented disease progression or the inability to tolerate the lowest dosing regimen per previous protocol of thalidomide and/or high-dose dexamethasone without grade 3 or 4 toxicity.

Official Title
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Open-Label, Single-Arm Study of the Safety and Efficacy of CC-5013 Monotherapy for Subjects With Multiple Myeloma: A Companion Study for Studies THAL-MM-003, CC-5013-MM-009, and CC-5013-MM-010

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: CC-5013
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand and voluntarily sign an informed consent form. Age ≥ 18 years at time of signing the informed consent form. Able to adhere to the study visit schedule and other protocol requirements Participants with multiple myeloma and were enrolled in either THAL-MM-003, CC-5013-MM-009, or CC-5013-MM-010 and discontinued study therapy with thalidomide and high-dose dexamethasone or high-dose dexamethasone alone due to: documented disease progression OR inability to tolerate the lowest dosing regimen allowed on previous protocol without a grade 3 or 4 toxicity. Eastern Cooperative Oncology Group (ECOG) performance status score 0,1,2 Recovery from thalidomide or dexamethasone-related toxicity to ≤ grade 2 (NCI CTC) Females of child-bearing potential (FCBP) must agree to using two methods of contraception Exclusion Criteria: Prior development of a ≥ grade 2 allergic reaction/hypersensitivity or prior development of a grade ≥ 3 rash or desquamation while taking thalidomide National Cancer Institute Common toxicity Criteria (NCI CTC) Use of any standard/experimental anti-myeloma therapy within 28 days of randomization or use of any experimental non-drug therapy within 56 days of initiation of drug treatment Any serious medical condition, laboratory abnormality, or psychiatric illness that will prevent the participant from signing the informed consent form or that will place the participant at an unacceptable risk for toxicity if he/she participates in the study. Pregnant or lactating females. Prior therapy with CC-5013; prior history of malignancies, other than multiple myeloma (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast), unless subject has been free of disease for ≥ 5 years More than 4 months has elapsed since the last dose of study drug was administered on study Tal MM-003, CC-5013-MM-009, CC-5013-MM-010 Absolute neutrophil count (ANC) <1,000cells/mm^3 (1.0 X 10^9/L) Platelet count <75,000/mm^3 (30 X 10^9/L) for those with <50% if the bone marrow nucleated cells re plasma cells; Platelet count <30,000/mm^3 (30 X 10^9/L) for those with <50% if the bone marrow nucleated cells re plasma cells Serum creatinine >2.5mg/dL; serum SGOT/AST or SGPT/ALT x upper limits of normal (ULN) Serum total bilirubin >2.0mg/d/L

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: Lenalidomide 25mg (CC-5013)<br>Oral 25mg daily on Days 1-21 every 28 days | Drug: CC-5013<br>* Oral 25mg daily on Days 1-21 every 28 days.<br>* Other names: lenalidomide;Drug: Lenalidomide<br>* Oral Lenalidomide 25mg daily on Days 1-21 every 28 days.<br>* Other names: CC-5013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE) During the Treatment Phase | An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which 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; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; | Until data cut-off of 22 Oct 2009; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. Maximum exposure to Lenalidomide treatment was 1260 days. | 
| Number of Participants With Adverse Events (AE) During the Extension Phase | An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which 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; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; | From 22 Oct 2009 to November 2013; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time to progression based on the myeloma response determination criteria developed by Bladé et al 1998 and is defined as the time from registration to the first documented progression. The progressive disease criteria included increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia. | Up to 70 months | 
| Myeloma Response Rate | Myeloma response determination criteria developed by Bladé et al 1998. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens. | Up to 70 months | 
| Duration of Response | Duration of response based on the Myeloma response determination criteria developed by Bladé et al 1998 and defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on International Myeloma Working Group (IMWG) criteria. | Up to 70 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Revlimid