A Study of Durvalumab in Combination With Lenalidomide With and Without Dexamethasone in Subjects With Newly Diagnosed Multiple Myeloma
This is a multicenter, open-label, Phase 1/2 study to determine the recommended dose and regimen of durvalumab in combination with lenalidomide (LEN) with and without dexamethasone (dex) in subjects with Newly diagnosed multiple myeloma (NDMM).
The study will consist of a dose-finding phase as well as a parallel dose-expansion phase to determine the optimal regimen.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1b Multicenter, Open-label Study to Determine the Recommended Dose and Regimen of Durvalumab (MEDI4736) (DUR) in Combination With Lenalidomide (LEN) With and Without Low-dose Dexamethasone (Dex) in Subjects With Newly Diagnosed Multiple Myeloma (NDMM)|
- Dose-limiting toxicities (DLTs) [ Time Frame: Approximately 1 month ]Dose-limiting toxicities will be evaluated during the DLT evaluation period for the subjects in the dose-finding portion of the study.
- Adverse Events (AEs) [ Time Frame: Up to approximately 2 year ]Number of participants with adverse events
- Overall Response Rate [ Time Frame: up to approximately 2 year ]Is defined as tumor response, based on the investigator assessments according to the International Myeloma Working Group (IMWG) Uniform Response Criteria
- Response Improvement Rate (RIR) [ Time Frame: Up to approximately 2 years ]Is defined as response improved from the assessment at the Cycle 1 Day1
- Time to Response (TTR) [ Time Frame: up to approximately 2 year ]Is defined as time from Cycle 1 Day1 to the first documentation of response
- Duration of Response (DOR) [ Time Frame: up to approximately 2 year ]Time from the first response to the first documentation of disease progression or death, whichever is earlier, based on the investigator assessments according to the IMWG Uniform Response Criteria
- Pharmacokinetic- Cmax [ Time Frame: approximately 1 year ]Maximum observed concentration
- Pharmacokinetic- AUC [ Time Frame: approximately 1 year ]Area under the concentration-time curve
- Pharmacokinetic- Tmax [ Time Frame: approximately 1 year ]Time to maximum concentration
- Pharmacokinetic- t1/2 [ Time Frame: approximately 1 year ]Terminal elimination half-life
- Pharmacokinetic- CL/F [ Time Frame: approximately 1 year ]Apparent total body clearance
- Pharmacokinetic- Vz/F [ Time Frame: approximately 1 year ]Volume of distribution
- Progression-Free Survival (PFS) [ Time Frame: Approximately 8 years ]Time from cycle 1 day 1 (C1D1) to the first documentation of disease progression or death from any cause during study, whichever occurs earlier
- Overall Survival(OS) [ Time Frame: Approximately 8 years ]Time from cycle 1 day 1 to death due to any cause
|Study Start Date:||April 2016|
|Estimated Study Completion Date:||August 2024|
|Estimated Primary Completion Date:||April 2022 (Final data collection date for primary outcome measure)|
Experimental: Cohort A for high risk transplant non-eligible NDMM subjects
||Drug: Durvalumab Drug: Lenalidomide Drug: Dexamethasone|
Experimental: Cohort B for ≥65 years old TNE NDMM non high risk subjects
||Drug: Durvalumab Drug: Lenalidomide Drug: Dexamethasone|
Experimental: Cohort C for high risk post-transplant NDMM subjects
||Drug: Durvalumab Drug: Lenalidomide|
The dose-finding phase will determine recommended dose (RD) for durvalumab in combination with lenalidomide (LEN) with and without dexamethasone (dex) in a 28-day treatment cycle. Three treatment Cohorts (A, B, and C) will be enrolled in parallel:
- Cohort A: durvalumab + LEN +dex on high risk Transplant non-eligible (TNE) Newly diagnosed multiple myeloma (NDMM) subjects;
- Cohort B: durvalumab + LEN +dex (Dex for up to 12 cycles) on ≥ 65 years old TNE NDMM subjects who are not high risk;
- Cohort C: durvalumab + LEN as maintenance on post-transplant high risk NDMM subjects; Based on experience with durvalumab for other indications, the initial dose of durvalumab will be 1500 mg for each treatment cohort. The dose of durvalumab might be de-escalated to 750 mg level.
The dose of LEN will be 25 mg (adjustable per the CrCl) value on Days 1 to 21 of each 28-day treatment cycle for subjects on Cohort A and B. The dose of LEN will be 10 mg on Days 1 to 21 of each 28-day treatment cycle for subjects on Cohort C.
The dose of dex will be 40 mg/day (for subjects ≤ 75 years old) or 20 mg/day (for subjects > 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle for Cohort A and Cohort B (for up to 12 cycles).
Initially, 6 subjects will be enrolled into each cohort and each will receive 1500 mg durvalumab.
The dose-limiting toxicity (DLT) evaluation period will be the first treatment cycle.
- If ≤ 1 of the 6 initial subjects experience a DLT within the first cycle, then the doseexpansion phase may be initiated with durvalumab 1500 mg as the recommended dose (RD);
- If 2 or more of the 6 initial subjects experience a DLT within the first cycle, then the maximum tolerated dose (MTD) has been exceeded and de-escalation to durvalumab 750 mg level after review of safety and PK/Pd of the initial 6 subjects by the DRT Any of the cohorts may be removed from the study based on emerging PK, Pd, efficacy or safety data.
Dose de-escalation will only occur after review of safety (DLT) and possibly PK/Pd data by the Dose Review Team ( DRT).
Note: In the US, two treatment arms (A and B) will be enrolled in parallel. Cohort C will enroll upon completion of at least 4 cycles of follow-up for safety assessment of Cohorts A and B.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02685826
|Contact: Associate Director Clinical Trial Disclosurefirstname.lastname@example.org|
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|Study Director:||Annette Ervin-Haynes, MPA||Celgene|