This study will evaluate the safety, tolerability and efficacy of elranatamab in patients with relapsed or refractory AL amyloidosis.
This is a Phase I/II, multi-center, open-label study designed to evaluate the safety, tolerability and efficacy of elranatamab in patients with relapsed or refractory light chain (AL) amyloidosis. Phase 1 will enroll 4-20 participants, beginning enrollment at Dose Level 0. If two or more participants at Level 0 experience DLT, dose will be decreased to Level -1. Each participant will complete the 28-day dose-limiting toxicity (DLT) evaluation period prior to dosing the next patient. Assuming a recommended phase 2 dose (RP2D) is found, Phase 2 will enroll an additional 29 participants for a total of 49 participants. Dose level 0 consists of: Cycle 1: 12 mg (D1)/32 mg (D4)/ 76 mg (D8, 15, 22); Cycle 2: 76 mg on D1, D8, D15 and D22. If \< VGPR after Cycle 2: Cycles 3-6: 76 mg on D1, 8, 15 and 22. If ≥ VGPR after Cycle 2: Cycles 3-6: 76 mg on D1 and 15 Dose Level -1 consists of: Cycle 1: 12 mg (D1)/32 mg (D4)/ 76 mg (D8, D22), Cycles 2-6: 76 mg D1 and D15
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Elranatamab administered subcutaneously for 6 cycles of treatment with 28 days in a treatment cycle
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGTo determine RP2D
The recommended phase 2 dose determined in phase 1
Time frame: up to 26 months
To evaluate objective response rate (ORR)
Defined as the proportion of patients with CR, VGPR, or PR, and will be provided as unconfirmed and confirmed ORR at the end of six cycles of treatment. Confirmed responses are those that persist on repeat imaging study at least 28 days after the initial documentation of response.
Time frame: up to 60 months
To assess safety and tolerability of elranatamab in patients with relapse or refractory AL amyloidosis
Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0
Time frame: up to 72 months
To assess best overall response (BOR)
BOR will be analyzed as the number of patients (percentage) with each response, divided by the number of patients treated.
Time frame: up to 72 months
To assess duration of response (DoR)
DoR will be analyzed using Kaplan-Meier method and is defined as the time from the first documentation of CR, VGPR, or PR to the first documentation of objective progression or death due to any cause. .
Time frame: up to 72 months
To assess progression-free survival (PFS)
Progression-free Survival (PFS) will be analyzed using Kaplan-Meier method and is defined as the time from Cycle 1 Day 1 to first documentation of objective progression (PD) or death due to any cause, whichever comes first.
Time frame: up to 72 months
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To assess overall survival (OS)
OS is defined as the time from the date of Cycle 1 Day 1 to date of death due to any cause.
Time frame: up to 72 months
Incidence and severity of cytokine release syndrome (CRS) and immune effector cell- associated neurotoxicity syndrome (ICANS)
Number of cases of CRS and ICANs and Grade of CRS and ICANs cases
Time frame: up to 72 months
Incidence of treatment emergent adverse events
Number of treatment- emergent AEs. An AE is treatment-emergent if the onset occurs on Cycle 1 Day 1 through 90 days after the last dose of investigational product.
Time frame: up to 72 months
To assess major organ deterioration (MOD) progression free survival (PFS) for the duration of the study
PFS is defined as the time from Cycle 1 Day 1 to first documentation of objective progression (PD) or death due to any cause, whichever comes first.
Time frame: up to 72 months