FT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL

FATE FT596 With Rituximab as Relapse Prevention in High Risk Patients After Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; NHL; High-grade B-cell Lymphoma
• Intervention / Treatment: Drug: FT596; Drug: Rituximab

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55401
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Siteman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FT596 + Rituximab Dose Level 1: 9x10^7 cells/dose; 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).	Drug: FT596; FT596 is given 2-3 days after rituximab; however, it may be delayed for up to 7 days until all rituximab infusion related toxicities resolve to ≤Grade 1.; Drug: Rituximab; Rituximab 375 mg/m^2 is administered as an IV infusion per institutional standard of care and package insert on 2-3 days (48 to 72 hours) prior to the FT596 infusion; Other Names: Rituxan
Experimental: FT596 + Rituximab Dose Level 2: 3x10^8 cells/dose; 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).	Drug: FT596; FT596 is given 2-3 days after rituximab; however, it may be delayed for up to 7 days until all rituximab infusion related toxicities resolve to ≤Grade 1.; Drug: Rituximab; Rituximab 375 mg/m^2 is administered as an IV infusion per institutional standard of care and package insert on 2-3 days (48 to 72 hours) prior to the FT596 infusion; Other Names: Rituxan
Experimental: FT596 + Rituximab Dose Level 3: 9x10^8 cells/dose; 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).	Drug: FT596; FT596 is given 2-3 days after rituximab; however, it may be delayed for up to 7 days until all rituximab infusion related toxicities resolve to ≤Grade 1.; Drug: Rituximab; Rituximab 375 mg/m^2 is administered as an IV infusion per institutional standard of care and package insert on 2-3 days (48 to 72 hours) prior to the FT596 infusion; Other Names: Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Dose Limiting Toxicity Events	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	28 Days Post FT596 infusion

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Dr.Veronika Bachanova, MD, PhD, Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2020
• Primary Completion (Actual): February 8, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: June 12, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Lymphoma; Stem cell transplantation; auto HSCT
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 2019LS230; P01CA111412 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No