This is a single center, single arm Phase Ib study with expansion cohort designed to establish the safety and physiologic effects of sirolimus pre-conditioning followed by T-cell engaging bispecific antibody therapy.
This is a Phase Ib trial with expansion cohort to assess the safety and estimate the preliminary efficacy of sirolimus pre-conditioning prior to treatment with a T-cell engaging bispecific antibody in patients with relapsed / refractory multiple myeloma previously exposed to T-cell engager therapy. Following Phase Ib, the study will enroll an expansion cohort to test the hypothesis that sirolimus pre-conditioning will result in an increase in the Teffector: Texhausted -cell ratio.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Sirolimus is an immunosuppressant drug. Sirolimus binds to FK binding protein 12 and inhibits mTOR. This then suppresses T-cell proliferation and inhibits progression from G1 to S phase of the cell cycle.
Teclistamab is a bispecific antibody that binds the CD3 receptor on T-cells and the B-cell maturation antigen on multiple myeloma cells and healthy B-lineage cells.
Talquetamab is a bispecific antibody that binds the CD3 receptor on T-cells and the GPRC5d receptor on multiple myeloma cells.
University of Iowa Health Care
Iowa City, Iowa, United States
RECRUITINGPhase Ib: Dose limiting toxicities (DLTs) as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
The incidence of treatment-emergent adverse events will be summarized by system organ class and/or preferred term, type of adverse event, severity (based on NCI CTCAE v5.0) grades), and relation to study treatment. The most severe grade per participant will be reported. Adverse events leading to premature discontinuation from the study intervention and serious treatment-emergent adverse events will be presented in tabular form.
Time frame: From treatment initiation through 30 days post last dose of study treatment
Expansion Cohort: Participants change in the Teffector: Texhausted cell ratio
Testing the null hypothesis H0: ΔPost-Pre = 0 versus the alternative H1: ΔPost-Pre ≠ 0. Results will be used as preliminary estimates to inform a subsequent larger trial.
Time frame: From treatment initiation through 3 months
Participant change in the following T-cell subsets: T-regulatory; T-Effector Memory (T-EM); T-Effector Memory expressing RA (T-EMRA)
The within participant change in the following T-cell subsets will be estimated: T-regulatory, T-EM, T-EMRA. Mixed effects regression models will be utilized to estimate changes. Random effects will be included to account for the longitudinally correlated nature of repeated measurements. Graphical plots of the estimated mean and associated 95% confidence intervals by time point in the study will be produced.
Time frame: From treatment initiation through 3 months
The proportion of participants with grade 3 or higher CRS
The rate of grade ≥3 CRS will be defined as the proportion of participants who develop grade 3 or higher CRS. The rate of grade ≥3 CRS will be reported as a binomial proportion along with a two-sided 95% confidence interval.
Time frame: From treatment initiation through 3 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The proportion of participants with grade 3 or highter ICANS
The rate of grade ≥3 ICAN will be defined as the proportion of participants who develop grade 3 or higher ICAN. The rate of grade ≥3 ICAN will be reported as a binomial proportion along with a two-sided 95% confidence interval.
Time frame: From treatment initiation through 3 months
The proportion of participants with a very good partial response (VGPR) or better at 3 months
The 3-month response rate will be defined as the proportion of participants with a very good partial response (VGPR) or better at 3 months. The 3-month response rate will be reported as a binomial proportion along with a two-sided 95% confidence interval.
Time frame: Three months after the initiation of treatment