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

• ClinicalTrials.gov Identifier: NCT00622336
• Recruitment Status: Completed
• First Posted: February 25, 2008
• Results First Posted: December 30, 2014
• Last Update Posted: November 20, 2019
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: CC-5013; Drug: Lenalidomide	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 330 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 1, 2003
• Actual Primary Completion Date: November 25, 2013
• Actual Study Completion Date: November 25, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lenalidomide 25mg (CC-5013); Oral 25mg daily on Days 1-21 every 28 days	Drug: CC-5013; Oral 25mg daily on Days 1-21 every 28 days.; Other Names: Revlimid; lenalidomide; Drug: Lenalidomide; Oral Lenalidomide 25mg daily on Days 1-21 every 28 days.; Other Names: Revlimid; CC-5013

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events (AE) During the Treatment Phase [ Time Frame: 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. ]
   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;
2. Number of Participants With Adverse Events (AE) During the Extension Phase [ Time Frame: From 22 Oct 2009 to November 2013; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. ]
   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;

Secondary Outcome Measures :

1. Time to Progression [ Time Frame: Up to 70 months ]
   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.
2. Myeloma Response Rate [ Time Frame: Up to 70 months ]
   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.
3. Duration of Response [ Time Frame: Up to 70 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Russian Federation

Republican Clinical Hospital #1

Izhevsk, Russian Federation, 426039

Nizhny Novgorod Clinical Hospital n.a.Semashko

Nizhny Novgorod, Russian Federation, 603126

Novosibirsk State Regional Clinical

Novosibirsk, Russian Federation, 630087

Samara Regional Clinical Hospital

Samara, Russian Federation, 443095

Ukraine

Kharkov Postgraduate Medical Academy Kharkov Regional Clinical

Kharkov, Ukraine, 61070

Institute of Hematology and Transfusiology of the UAMS Department of blood diseases

Kiev, Ukraine, 04060

Odessa Regional Clinical Hospital

Odessa, Ukraine, 65025

Sponsors and Collaborators

Celgene

Investigators

• Study Director: Robert Knight, MD; Celgene Corporation

More Information

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00622336
• Other Study ID Numbers: CC-5013-MM-012; 2004-002102-30 ( EudraCT Number )
• First Posted: February 25, 2008
• Results First Posted: December 30, 2014
• Last Update Posted: November 20, 2019
• Last Verified: November 2019

Keywords provided by Celgene:

Multiple Myeloma; Revlimid

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lenalidomide; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents