This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL.
This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL. The study consists of a Dose Escalation phase followed by a Dose Expansion phase. In the Dose Escalation phase, subjects will be enrolled in 1 of 7 dose levels, starting with 60 µg/kg and up to 720 µg/kg. A dose schedule for an individual dose level will not be taken into expansion until the Dose Escalation phase has been completed or a maximum tolerated dose (MTD) has been determined, whichever occurs first. In the Dose Expansion phase, up to 15 subjects will be enrolled and treated with the recommended dose identified in the Dose Escalation phase. Up to 17- 42 subjects in the Dose Escalation phase, and up to 15 subjects in the Dose Expansion phase will be enrolled at approximately 20 study centers. Treatment Plan: NT-I7 (aka rhIL-7-hyFc, efineptakin alpha), Tisagenlecleucel (Kymriah®), Axicabtagene ciloleucel (Yescarta®), Lisocabtagene Maraleucel (Breyanzi®) \*CAR-T Therapy will be administered per manufacturer's recommendations and in accordance with FDA prescribing guidelines and best institutional practices for standard of care use.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
NT-I7 is administered via an intramuscular injection after CAR-T infusion on Day 21.
Administered as standard of care as described in the package insert on Day 0.
Administered as standard of care as described in the package insert on Day 0.
City of Hope
Duarte, California, United States
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
Detroit, Michigan, United States
Washington University in St. Louis
St Louis, Missouri, United States
Duke Cancer Institute
Durham, North Carolina, United States
For Dose Escalation Phase: Incidence of adverse events (AE)
According to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: 21 Days
Incidence of Dose Limiting Toxicities (DLT)
DLT is defined as any AE occurring within the first 21 days after NT-I7 injection that is considered to be at least possibly, probably, or definitely related to the study treatment (NT-I7) per the investigator, and that meets at least one of the non-hematologic or hematologic criteria listed below.
Time frame: 21 Days
To determine the Maximum Tolerated Dose (MTD)
The MTD will be defined as the dose of NT-I7 that yields a DLT rate ≤ 33%.
Time frame: 21 Days
To determine the Recommended Phase 2 Dose (RP2D)
Determination of the RP2D: The RP2D will be based on an accumulation of all available data. All available data including clinical Pharmacokinetic, Pharmacodynamic, anti-tumor activity (including best overall response rate) and safety, and nonclinical pharmacology data will be pooled. Integrated dose-response and exposure-response analyses will be conducted to determine the RP2D
Time frame: 21 Days
Measurement of Duration of Response (DOR)
Duration of Response (DoR) for the responders defined as the time from the first occurrence of a documented objective response (Partial Response \[PR\] or Complete Response \[CR\]) to the time of the first documented disease progression or death from any cause, whichever occurs first, per the Lugano classification as determined by the investigator.
Time frame: up to 3 months
Measurement of Progression-Free Survival (PFS)
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Administered as standard of care as described in the package insert on Day 0.
Progression Free Survival (PFS) defined as the time from the first study treatment (Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per the Lugano classification as determined by the investigator.
Time frame: up to 3 months
Measurement of Overall Survival (OS)
Overall survival (OS) defined as the time from first study treatment (Day 1) to death from any cause.
Time frame: up to 3 months
Rates of grade 3 and higher cytokine release syndrome (CRS)
Grading of CRS will be based on American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.
Time frame: Up to 3 months
Rates of grade 3 and higher immune effector cell associated neurotoxicity syndrome (ICANS)
Grading of ICANS will be based on American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.
Time frame: Up to 3 months
The effect of NT-I7 on CAR-T cells expansion by Quantitative DNA Polymerase Chain Reaction (PCR)
Time frame: Up to 3 months
The effect of NT-I7 on CAR-T cells expansion by fluorescence-activated cell sorting (FACS)
Time frame: Up to 3 months