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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00622336
• Other study ID #: CC-5013-MM-012
• Secondary ID: 2004-002102-30
• Status: Completed
• Phase: Phase 3
• Start date: April 1, 2003
• Est. completion date: November 25, 2013

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: November 25, 2013
• Est. primary completion date: November 25, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• CC-5013
Oral 25mg daily on Days 1-21 every 28 days.
• Lenalidomide
Oral Lenalidomide 25mg daily on Days 1-21 every 28 days.

Locations

Country	Name	City	State
Russian Federation	Republican Clinical Hospital #1	Izhevsk
Russian Federation	Nizhny Novgorod Clinical Hospital n.a.Semashko	Nizhny Novgorod
Russian Federation	Novosibirsk State Regional Clinical	Novosibirsk
Russian Federation	Samara Regional Clinical Hospital	Samara
Ukraine	Kharkov Postgraduate Medical Academy Kharkov Regional Clinical	Kharkov
Ukraine	Institute of Hematology and Transfusiology of the UAMS Department of blood diseases	Kiev
Ukraine	Odessa Regional Clinical Hospital	Odessa

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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
Secondary	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
Secondary	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