FT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL

Phase 1

Completed

• Conditions: NHL; Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma
• Interventions: Drug: FT596; Drug: Rituximab

• Registration Number: NCT04555811
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary

This is a Phase I multi-center study to evaluate the safety of FT596 when given with rituximab as relapse prevention in patients who have undergone an autologous hematopoietic stem cell transplant (auto-HSCT) for diffuse large or high-grade B cell lymphoma.

Detailed Description

This study uses a single dose of the investigational product FT596 in the early post-transplant period. Rituximab or an FDA approved by biosimilar including Rituxan®, Truxima®, and Ruxience™ is given 48 to 72 hours prior to FT596. The goal of this study is to 1) establish a maximum tolerated dose (MTD) of FT596 when given 30 days after transplant and 2) to confirm the MTD and safety of giving a single dose of FT596 at Day 7 post-transplant starting at one dose level below the MTD identified at Day 30.

Study Timeline

• Study First Submitted: 2020-09-14
• Study First Submitted QC: 2020-09-14
• Study First Posted: 2020-09-21
• Study Start: 2020-09-22
• Primary Completion: 2023-02-08
• Study Completion: 2023-11-30
• Results First Submitted: 2024-02-27
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-12
• Last Update Submitted: 2024-06-12
• Results First Posted: 2024-07-09
• Last Update Posted: 2024-07-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• Diagnosis of diffuse large B cell lymphoma or aggressive (high-grade) B-cell lymphoma for which an autologous stem cell transplant is planned or recently completed

• High risk for relapse defined as at least one of the below:

  • Primary induction failure (no complete or partial remission at any point after diagnosis
  • Initial remission duration < 12 months
  • Lack of complete metabolic (PET scan) response after 2-3 cycles of salvage chemotherapy
  • Evidence of c-myc and bcl-2 and/or bcl-6 re-arrangement (double hit or triple hit lymphoma)
  • Age-adjusted IPI 2-3 at relapse

• Age 18 years or older at the time of signing consent.

• Agrees to use adequate contraception (or evidence of sterility) for at least 12 months after the last dose of rituximab.

• Agrees and signs the separate consent for up to 15 years of follow-up (Long-term Follow-up study CPRC#2020LS052)

• Provides voluntary written consent prior to the performance of any research related activities.

Exclusion Criteria

• Receipt of any investigational therapy within 28 days prior to the first dose of FT596 or planned use of an investigational therapy during the first 100 days after transplant
• Planned post-transplant irradiation prior to Day +100
• Seropositive for HIV, active Hepatitis B or C infection with detectable viral load by PCR
• Body weight <50kg
• Known allergy to the following FT596 components: albumin (human) or DMSO
• Unable to receive rituximab

Post-HSCT Reconfirmation of eligibility

• No life-threatening medical issues (i.e. ongoing Grade 4 adverse events) where, in the opinion of the treating investigator, use of FT596 is not in the patient's best interest.

• No active uncontrolled infection.

• Adequate organ function post-transplant including:

  • alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x ULN (Grade 2 CTCAE v5)
  • total bilirubin ≤1.5 x ULN (Grade 1 CTCAE v5)
  • serum creatinine ≤1.5 x ULN (Grade 1 CTCAE v5)
  • oxygen saturation ≥93% on room air

• For Day 30 dosing only - CBC requirement consistent with engraftment (ANC>500, platelet>20,000 without transfusion support within previous 7 days). There are no CBC parameters for Day 7 dosing.

• No requirement for systemic immunosuppressive therapy (> 5mg prednisone daily) during the FT596 dosing period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
FT596 + Rituximab Dose Level 1: 9x10^7 cells/dose	FT596	Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM).
FT596 + Rituximab Dose Level 1: 9x10^7 cells/dose	Rituximab	Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM).
FT596 + Rituximab Dose Level 2: 3x10^8 cells/dose	FT596	Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM).
FT596 + Rituximab Dose Level 3: 9x10^8 cells/dose	FT596	Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM).
FT596 + Rituximab Dose Level 2: 3x10^8 cells/dose	Rituximab	Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM).
FT596 + Rituximab Dose Level 3: 9x10^8 cells/dose	Rituximab	Up to three sequential FT596 dose levels are planned for Day 30 administration: (Dose Level 1: 9x10\^7 cells/dose, Dose Level 2: 3x10\^8 cells/dose, Dose Level 3: 9x10\^8 cells/dose with a Dose Level -1: 3x10\^7 cells/dose tested only if dose limiting toxicity events (DLT) occur at dose level 1).The maximum tolerated dose will be determined by using a modified continual reassessment method (CRM).

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Dose Limiting Toxicity Events	28 Days Post FT596 infusion	The component I design (FT596 on day 30) will continue until the MTD is declared or until the first dose is declared to be above MTD. The component I dose limiting toxicity (DLT) is defined as any of the following events within 28 days after the FT596 dosing based on CTCAE v5:Grade 4 hematologic toxicity lasting \> 7 days ,Grade 4 non-hematologic toxicity ,Grade ≥3 Infusion Related Reaction, Grade 2 acute GVHD that requires steroid therapy \>7 days or progression after 3 days of steroids or has partial response after 14 days of treatment, Grade ≥3 acute GVHD, Grade 4 cytokine release syndrome (CRS), Grade 3 CRS that does not resolve to \< Grade 2 in 72 hours, Grade 3 neurotoxicity, Grade 3 organ toxicity involving vital organs, Any Grade 3 non-hematological toxicity that does not resolve to ≤Grade 2 within 72 hours

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival 12 Months Post Auto-HCT	12 Months Post Auto-HCT	Progression-Free Survival 12 Months Post Auto-HCT
Number of Participants Experiencing Adverse Events	1 year post FT596 infusion	Number of participants experiencing adverse events related to FT596 post auto-HSCT in combination with rituximab
Percentage of Participants With Relapse/Progression	1 year post auto HSCT	Percentage of participants experiencing progression or relapse at 12 months post auto HSCT
Number of Participants Experiencing Non-relapse Mortality Incidents at 100 Days Post HSCT	100 days post HSCT	Number of participants experiencing non-relapse mortality at 100 days post auto-HSCT.
Percentage of Non-relapse Mortality Incidents at One Year Post HSCT	one year post auto-HSCT	Percentage of participants experiencing non-relapse mortality at one year post auto-HSCT.

Trial Locations

Locations (2)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Washington University School of Medicine - Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States