Relapsed and refractory multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
Celgene International II Sàrl
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject received at least 3 prior anti-myeloma regimens including a PI and an immunomodulatory agent or is double-refractory to a PI and an immunomodulatory agent. · Induction, bone marrow transplant with or without maintenance therapy is considered one regimen. · Refractory is defined as disease that is nonresponsive on therapy, or progresses within 60 days of last therapy. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy. · For subjects who received more than 1 regimen containing a PI their disease must be refractory to the most recent PI containing regimen. · For subjects who received more than 1 regimen containing an immunomodulatory agent their disease must be refractory to the most recent immunomodulatory agent containing regimen. 2. Subject has measurable disease defined as: a. M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis (uPEP): sPEP = 0.5 g/dL or uPEP = 200 mg/24 hours) and/or b. Light chain MM without measurable disease in the serum or the urine: serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio. 3. Subject achieved a response (MR or better) to at least 1 prior treatment regimen. 4. Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen. 5. Subject received an alkylating agent alone or in combination with other myeloma treatment. 6. Subject has an Eastern Cooperative Oncology Group performance-status score of 2 or less. 7. Subject’s toxicities resulting from previous therapy (including peripheral neuropathy) have resolved or stabilized to = Grade 1. 8. Subject is at least 18 years of age at the time of signing the informed consent form (ICF). 9. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 10. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 11. Females of childbearing potential (FCBP ) must: a. Have 2 negative pregnancy tests as verified by the investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact. b. Either practice true abstinence2 from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study treatment, during the study therapy (including dose interruptions), and for at least 90 days after discontinuation of study treatment. c. Refrain from egg cell donation for at least 90 days after the final dose of DURVA or DARA, whichever is later. 12. Male subjects must: a. Either practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following study treatment discontinuation, even if he has undergone a successful vasectomy. b. Refrain from sperm donation for at least 90 days after the final dose of DURVA or DARA, whichever is later. Are the trial subjects under 18? no Number of subjects for this
Exclusion criteria
Exclusion criteria: 1. Subject has had prior exposure to anti-CTLA-4, anti-PD-1, anti-PD-L1 mAbs, cell-based therapies, or cancer vaccines 2. Subject received DARA or other anti-CD38 antibodies therapies previously 3. Subject received any of the following within the last 14 days of initiating study treatment: a. Plasmapheresis b. Major surgery (as defined by the investigator) c. Radiation therapy other than local therapy for myeloma associated bone lesions d. Use of any systemic anti-myeloma drug therapy 4. Subject received prior treatment with a monoclonal antibody within 5 half-lives of initiating study treatment 5. Subject used any investigational agents within 28 days or 5 half-lives of initiating study treatment 6. Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment 7. History of organ or allogeneic stem cell transplantation 8. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks before the date of randomization 9. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) 13.5 mg/dL (> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase(ALT) > 2.5 × upper limit of normal (ULN) g. Serum total bilirubin > 1.5 × upper limit of normal (ULN) or > 3.0 mg/dL for subjects with documented Gilbert’s syndrome 10. Subject has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS MM 11. Subject has known COPD with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal 12. Subject has known moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification 13. Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or amyloidosis 14. Subject has nonsecretory MM 15. Subject has known allergy or hypersensitivity to study drug formulations 16. Subject has active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: a. Subjects with vitiligo or alopecia. b. Subjects with hypothyroidism stable on hormone replacement. c. Psoriasis not requiring systemic treatment. 17. Subject has history of primary immunodeficiency 18. Subject is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C 19. Subject has received live, attenuated vaccine within 30 days prior to the first dose of DURVA 20. Subject is currently using or has used immunosuppressive medication within 14 days prior to the first study dose of study treatment. The following are exceptions to this criterion: a. Intranasal, inhaled, or local steroid injections b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent c. Steroids as premedication for hypersensitivity reactions 21. Subject has any one of the following: a. Clinically significant abnormal ECG finding at screening b. Congestive heart failure c. Myocardial infarction within 12 months prior to starting study treatment d. Unstable or poorly controlled angina
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and efficacy of DURVA and DARA in subjects with RRMM;Secondary Objective: - Evaluate additional measures of efficacy (time-to-response, duration of response, progressive-free survival) of DURVA and DARA in subjects with RRMM; - Evaluate the pharmacokinetics (PK) of DURVA and DARA in subjects with RRMM.;Primary end point(s): - Overall response rate (ORR): tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria. - Safety: type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment.;Timepoint(s) of evaluation of this end point: Overall response rate: Tumor response, including PD, will be assessed by the investigators using the IMWG criteria. The ORR will be calculated as the percent of responders (count of subjects with at least a PR, divided by the number of subjects in the EE Population). The ORR together with the proportions in each response category based on the IMWG criteria will be tabulated by dose cohort and arm. A 95% confidence interval of the ORR of D2 for all subjects treated with the RP2D and an 80% confidence interval of the ORR of exploratory PD3cohort will be provided. AEs: At screening and Continuously, until 90 days after last dose of DURVA or DARA, whichever is later | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time-to-response (TTR): time from enrollment to the first documentation of response (Partial Response [PR] or greater). - Duration of response (DOR): time from the first documentation of response (PR or greater) to the first documentation of PD. - Progression-free survival (PFS): time from enrollment to the first documentation of PD or death from any cause during study, whichever occurs earlier. PK parameters: Typical serum/plasma PK parameters for DURVA and DARA, such as maximum observed concentration (Cmax), area under the concentration-time curve (AUC), time to maximum concentration (Tmax), terminal elimination half-life (t1/2), clearance (CL/F), and volume of distribution (Vz/F).;Timepoint(s) of evaluation of this end point: - The PK sampling time points for DURVA in Phase 2 Stage 1 (including subjects enrolled in the D2 safety run-in phase) will be as follows: • C1D2: predose (-30 to -5 minutes prior to dose), end of infusion (EOI) (+30 minutes), •C1D8, • C1D15, • C1D22. • Additional Durvalumab PK samples to be collected to match immunogenicity collections predose (-30 to -5 minutes prior to dose) on C2D1, C4D1, C6D1, C10D1, and C14D1 and EoT. The PK sampling time points for DARA in Phase 2 Stage (including subjects enrolled in the D2 safety run-in phase) will be as follows: • C1D1, C1D8, C1D15, C1D22: predose (-30 to -5 minutes prior to dose), and EOI (+30 minutes) • EOT, • 28 days after EOT, • 90 days after last DARA or DURVA dose. | — |
Countries
Belgium, Canada, Denmark, France, Germany, Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed