Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 3:24 AM
Ignite Modification Date:
2025-12-25 @ 3:24 AM
NCT ID:
NCT02716805
Brief Summary:
This was a Phase 1, open-label, multicenter, study of checkpoint inhibitor therapy (tremelimumab ± durvalumab) prior to and following autologous stem cell transplant (ASCT) and high-dose melphalan in subjects with multiple myeloma who were at a high risk for relapse, were eligible for ASCT, and had available cryopreserved stem cells. Primary study objectives were to determine the safety and tolerability of study treatment. Further objectives were to evaluate the clinical efficacy and biologic activity of the regimen.
Detailed Description:
Eligible subjects were to be enrolled sequentially into one of 4 treatment cohorts (beginning with Cohort 1) to receive pretreatment with Prevnar-13 on Day -33 ± 2 days, followed by a single dose of tremelimumab (75 mg) administered either alone (Cohorts 1 and 2) or in combination with a single dose of durvalumab (1500 mg; Cohorts 3 and 4) on Day -31 (approximately 21 days prior to steady-state leukopheresis for the collection of autologous peripheral blood lymphocytes \[PBLs\]). Leukopheresis was performed on Days -10 to -3, followed by high dose therapy (HDT) comprising melphalan (200 mg/m\^2) administered intravenously (IV) on Day -2, and ASCT using previously banked hematopoietic stem cells on Day 0. Autologous PBLs were re-infused into subjects on Day +3 following ASCT, with a single dose of tremelimumab (75 mg) administered on the same day. Following HDT/ASCT, treatment was to resume with tremelimumab (75 mg) administered either alone (Cohorts 1 and 2) or in combination with durvalumab (1500 mg; Cohorts 3 and 4) for the first 2 cycles following HDT/ASCT according to the following schedule.
Late post-ASCT treatment:
* Cohort 1: tremelimumab (75 mg) administered alone on Day 100 (±10) and 4 weeks later (Cycles 1 and 2)
* Cohort 3: tremelimumab (75 mg) + durvalumab (1500 mg) administered on Day 100 (±10) and 4 weeks later (Cycles 1 and 2)
Early post-ASCT treatment:
* Cohort 2: tremelimumab (75 mg) administered alone on Days 30 through 40 and Day 100 (±10) (Cycles 1 and 2)
* Cohort 4: tremelimumab (75 mg) + durvalumab (1500 mg) administered on Days 30 through 40 and Day 100 (±10) (Cycles 1 and 2)
For Cycles 3 through 8, durvalumab alone (1500 mg every 4 weeks) was to be administered in all cohorts.
Within each cohort, the second subject did not start treatment until the first subject had completed early engraftment (approximately Day 12 to 18 post-ASCT); therefore, the first subject in each cohort received the first dose of tremelimumab ± durvalumab and was observed for toxicity for approximately 7 weeks prior to enrollment of the second subject.
Protocol-specified dose-limiting toxicities (DLTs) were assessed from the first dose of study treatment up to and including Cycle 2 dosing (Day 128 for Cohorts 1 and 3 or Day 100 for Cohorts 2 and 4). Subjects were not to be treated in a new cohort until all subjects in the previous cohort had completed the DLT evaluation period and ≤ 1 of 6 subjects had experienced DLT.
After enrollment of 6 subjects in Cohort 1, the study was placed on partial clinical hold by the Food and Drug Administration (FDA) due to safety signals observed in other studies investigating pembrolizumab, an anti-programmed cell death-1 (PD-1) antibody, in combination with immunomodulatory agents in subjects with multiple myeloma. As a result, the single subject who was receiving durvalumab during Cycles 3 to 8 discontinued study treatment after Cycle 5; durvalumab was not initiated in the 4 subjects who remained in the study; and no further subjects were enrolled. Upon recommendations from the two Principal Investigators and the study chair, the 4 ongoing subjects, who were in the transplant phase of the study, were permitted to continue post-ASCT tremelimumab treatment after being re-consented under an intermediate expanded access protocol.
Study:
NCT02716805
Study Brief:
Protocol Section:
NCT02716805