Relapsed and/or Refractory Multiple Myeloma MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Elotuzumab
Product Code: HuLuc63
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Elotuzumab
CAS Number: 915296-00-3
Current Sponsor code: BMS-901608
Other des
Anti-CS1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Trade Name: Thalidomide Celgene 50 mg hard capsules
Product Name: Thalidomide Celgene 50 mg hard caps
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Subject is, in the investigator?s opinion, willing and able to comply with the protocol requirements. b) Subject has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care. 2) Target Population a) Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 for the TdE safety-lead in cohort; performance status of 0 - 2 for additional subjects. b) Confirmed diagnosis of previously treated multiple myeloma with documented progression by IMWG criteria after or during the most recent therapy. There is no limit to the number of prior lines of therapy. c) Measurable disease as defined by at least one of the following: i) Serum IgG, IgA or IgM M-protein >or= 0.5 g/dL, or serum IgD M-protein >or= 0.05 g/dL, OR ii) Urine M protein >or= 200 mg excreted in a 24-hour collection sample; OR iii) Involved serum free light chain level >or= 10 mg/dL provided the free light chain ratio is abnormal 3) Age and Reproductive Status a) Men and women, age >or= 18 years or legal age of consent per local regulations b) Women of childbearing potential (WOCBP) must use highly effective methods of birth control for at least 4 weeks before study treatment, throughout the study, even in the setting of dose interruptions, and for 3 months after the last dose of study treatment to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 90 days after dosing has been completed. Contraceptive methods must include at least one highly effective method AND one additional effective barrier method. The use of IUDs shall be at the discretion of the investigator. Hormonal contraceptives may not be used for contraception unless a drug-drug interaction study has demonstrated that the PK of the hormone based contraceptive has not been adversely affected. The use of hormone based contraceptives is not otherwise restricted. c) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the first dose of investigational product. d) Women must not be breastfeeding. e) Subjects must be willing to refrain from blood donations during study drug therapy and for 90 days after therapy. f) Men must agree to use a latex condom during sexual contact with a pregnant woman or with a WOCBP during treatment and for 1 week after dose interruption and/or cessation of treatment, even if they have had a successful vasectomy, and must agree not to donate sperm during study drug therapy and for 90 days after therapy. g) All subjects must follow instructions for birth control for the entire duration of the study and a minimum of 90 days after dosing has been completed. 4) Pharmacogenetic To participate in the Pharmacogenetic Sample Amendment, subjects must provide a signed Pharmacogenetic Blood DNA informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1) Target Disease Exceptions a) Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia. b) MGUS, smoldering myeloma or Waldenström?s macroglobulinemia. c) Active plasma cell leukemia (defined as either 20% of peripheral WBC comprised of plasma/CD138+ cells or an absolute plasma cell count of 2 x 109 /L). d) Subjects with non-secretory myeloma. 2) Medical History and Concurrent Diseases a) Any medical conditions that, in the investigator?s opinion, would impose excessive risk to the subject. Examples of such conditions include: i) Any uncontrolled disease, such as pulmonary disease, infection, or seizure disorder ii) Any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent b) Significant cardiac disease as determined by the investigator, including: i) Known or suspected cardiac amyloidosis; ii) Congestive heart failure of Class III or IV of the NYHA classification; iii) Uncontrolled angina, hypertension, or arrhythmia; iv) Myocardial infarction in past 6 months; v) Any uncontrolled or severe cardiovascular disease vi) Prior cerebrovascular event with persistent neurologic deficit c) Prior or concurrent malignancy, except any malignancy from which the subject has been disease-free for >or= 5 years d) Known HIV infection e) Active hepatitis A, B, or C f) Uncontrolled diabetes g) Grade >or= 2 neuropathy. h) Any residual AEs from prior chemotherapy, surgery, or radiotherapy that have not resolved to or= 11.5 mg/dL within 2 weeks of enrollment (despite appropriate measures such as hydration, a short course of steroids, bisphosphonates, or calcitonin). b) Absolute neutrophil count or= 30 mL/minute). f) Total bilirubin > 1.5 x ULN. g) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >or= 3 x ULN. 4) Prior Therapy or Surgery a) Major surgery within 4 weeks or radiation therapy within 2 weeks prior to Cycle 1 Day 1 (localized radiation therapy for palliative treatment acceptable). b) Administration of chemotherapy, biological, immunotherapy, or investigational agent (therapeutic or diagnostic) within 3 weeks prior to Cycle 1 Day 1 (14 days for non-myelosuppressive therapy). Subjects should be 6 weeks from last dose of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and tolerability of Thalidomide-dexamethasone-Elotuzumab (TdE) in subjects with relapsed and/or refractory MM as assessed by the incidence of severe (Grade 3 or higher) non-hematologic adverse events (AEs).;Secondary Objective: To determine the frequency of dose modifications due to AEs in subjects with relapsed/refractory multiple myeloma treated with TdE. Exploratory Objectives: ? To evaluate the general safety of the TdE regimen ? To evaluate the clinical activity of TdE as defined by the modified International Myeloma Working Group (IMWG) response criteria ? To characterize the PK and immunogenicity of elotuzumab ? To assess safety and clinical activity of TdEC in those subjects who have a suboptimal response to TdE. Pharmacogenetic research objective: To study the association between genetic variation and drug response. Bristol-Myers Squibb may also use the DNA to study the causes and further progression of multiple myeloma.;Primary end point(s): The primary endpoint of this study is the proportion of subjects who experience one or more severe (Grade 3 or higher) non-hematologic AEs in subjects receiving TdE for relapsed/refractory MM;Timepoint(s) of evaluation of this end point: Evaluations will be conducted on all treated subjects over the TdE treatment period. The TdE treatment period is defined as the duration from the first dose of the study drug until the earlier of discontinuation from TdE or the time when cyclophosphamide is initiated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? The general safety endpoints are serious and non-serious AEs, clinical laboratory tests, and vital sign measurements. ? Efficacy Endpoints will be assessed based on the modified IMWG criteria. Objective Response Rate (ORR) Time to Response (TTR) Duration of Response (DOR) ? Pharmacokinetics of Elotuzumab ? The immunogenicity endpoints are serum titer values and the presence of anti?elotuzumab antibodies;Timepoint(s) of evaluation of this end point: Safety and Efficacy Evaluations will be conducted on all treated subjects over the TdE treatment period. Every 4 weeks from date of first dose of study drug on Cycle 1 Day 1 until progression on TdEC. Pharmacokinetics and immunogenicity will be evaluated in cycles 1,2,3,4 and 6 and since then, every 3 cycles, until end of treatment and 30 and 60 days of follow-up | — |
Countries
Spain
Contacts
Public ContactEU Start Up Department
Bristol-Myers Squibb International Corporation
Outcome results
None listed