NCT04714372

FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia

Study of FT538 in Combination With Daratumumab in Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This Phase I open-label dose escalation study is conducted in two stages with a primary endpoint to identify the maximum tolerated dose (MTD) of FT538 when administered with daratumumab in patients 12 years and older with advanced acute myeloid leukemia (AML) and related myeloid diseases.

Detailed description

FT538 is an off the shelf product comprised of allogeneic natural killer (NK)-cell immunotherapy lacking CD38 and expressing hnCD16 and IL-15RF. Daratumumab is a targeted therapy (IgG1k human monoclonal antibody) that targets CD38. FT538 is administered once a week for 3 consecutive weeks (Day 1, Day 8, and Day 15). Up to 5 dose levels will be tested. Fixed dose subcutaneous daratumumab is given on Day -12 and Day 5 prior to the NK cells as lymphodepletion, and on Day +3, Day +10, and Day +17 to maximize targeting. A short course of outpatient lymphodepleting chemotherapy is given on Day -4 and Day -3 to promote adoptive transfer. Day 1, the day of the 1st FT538 infusion, must be a Monday. The primary analysis for Phase I is intent-to-treat in that all patients receiving the 1st infusion of FT538 are evaluable for toxicity and efficacy. Patients who discontinue therapy prior to the first FT538 will be replaced. There are five potential FT538 dose cohorts. The starting dose is FT538 1x10e8 cells per dose with a lower safety dose of 5x10e7 if needed (Dose Level -1). The subsequent planned FT538 cohorts are 3x10e8, 1x10e9, and 1.5 x10e9 FT538 cells per dose. Dosing is based on hnCD16 expression, where 90% ± 10% of administered FT538 cells express hnCD16. The trial is conducted with no intra-patient escalation.

Conditions

• Acute Myeloid Leukemia
• Myeloid Leukemia
• Monocytic Leukemia

Interventions

Type	Name	Description
DRUG	Daratumumab/rHuPH20	Daratumumab 1800 mg co-formulated with 30,000 units of hyaluronidase (rHuPH20) given subcutaneously into subcutaneous tissue of the abdomen approximately 3 inches \[7.5 cm\] to the right or left of the navel over approximately 3-5 minutes on Day -12 and Day -5 prior to the 1st FT538 infusion, and on Day +3, Day+10, and Day+17 approximately 48 hours after each FT538 infusion.
DRUG	FT538	FT538 is administered as an IV infusion via gravity using an IV administration set with an in-line filter at the patient's assigned dose levels (DL) on Day 1, Day 8, and Day 15
DRUG	Fludarabine	Fludarabine 25 mg/m\^2 is administered as a 1 hour intravenous (IV) infusion per institutional guidelines once a day on 2 consecutive days (Day -4, and Day -3).
DRUG	Cyclophosphamide	Cyclophosphamide 300 mg/m\^2 is administered as a 2 hour intravenous (IV) infusion per institutional guidelines once a day on the same days that fludarabine is given.

Timeline

• Start date: 2021-11-03
• Primary completion: 2024-01-09
• Completion: 2024-10-15
• First posted: 2021-01-19
• Last updated: 2024-10-24
• Results posted: 2024-10-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study