FT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL

University of Minnesota (UMN)

Status and phase: Completed; Phase 1

Conditions: NHL; High-grade B-cell Lymphoma; Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma

Treatments: Drug: FT596; Drug: Rituximab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04555811

2019LS230

P01CA111412 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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7 participants in 3 patient groups

FT596 + Rituximab Dose Level 1: 9x10^7 cells/dose

Experimental group

Description:

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).

Treatment:

Drug: Rituximab

Drug: FT596

FT596 + Rituximab Dose Level 2: 3x10^8 cells/dose

Experimental group

Description:

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).

Treatment:

Drug: Rituximab

Drug: FT596

FT596 + Rituximab Dose Level 3: 9x10^8 cells/dose

Experimental group

Description:

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).

Treatment:

Drug: Rituximab

Drug: FT596