FT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL

NCT04555811 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2019LS230P01CA111412
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

auto HSCT; Stem cell transplantation; Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of Participants Experiencing Adverse Events

  1 year post FT596 infusion

• Percentage of Participants With Relapse/Progression

  1 year post auto HSCT

• Number of Participants Experiencing Non-relapse Mortality Incidents at 100 Days Post HSCT

  100 days post HSCT

• Percentage of Non-relapse Mortality Incidents at One Year Post HSCT

  one year post auto-HSCT

• Progression-Free Survival 12 Months Post Auto-HCT

  12 Months Post Auto-HCT

Study Arms (3)

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

EXPERIMENTAL

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; Drug: Rituximab

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

EXPERIMENTAL

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; Drug: Rituximab

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

EXPERIMENTAL

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; Drug: Rituximab

Interventions

FT596 DRUG

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.

FT596 + Rituximab Dose Level 1: 9x10^7 cells/dose; FT596 + Rituximab Dose Level 2: 3x10^8 cells/dose; FT596 + Rituximab Dose Level 3: 9x10^8 cells/dose

Rituximab DRUG

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

Also known as: Rituxan

FT596 + Rituximab Dose Level 1: 9x10^7 cells/dose; FT596 + Rituximab Dose Level 2: 3x10^8 cells/dose; FT596 + Rituximab Dose Level 3: 9x10^8 cells/dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55401, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Veronika Bachanova MD, PhD
• Organization: University of Minnesota, Masonic Cancer Center

bach0173@umn.edu

612-625-5469

Study Officials

• Dr.Veronika Bachanova, MD, PhD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients are enrolled in cohorts of 3 starting at Dose Level 1. There are three dose escalating doses of FT596. A minimum of 28 days will separate each cohort. For Dose Level 1 a minimum of 28 days will separate each patient to assess for dose limiting toxicity (DLT). In subsequent cohorts, the 1st and 2nd patient will be separated by at least 28 days and at least 14 days will separate the 2nd and 3rd patient. Each new cohort of three patients will be sequentially assigned to the most appropriate dose based on the updated toxicity probabilities under the continuous reassessment method (CRM), and the MTD will be identified when the total sample size of 18 is exhausted or 6 patients are sequentially enrolled at the same dose.

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 21, 2020
• Study Start: September 22, 2020
• Primary Completion: February 8, 2023
• Study Completion: November 30, 2023
• Last Updated: July 9, 2024
• Results First Posted: July 9, 2024

Record last verified: 2024-06

Locations

US (2)