FT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
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
- establish a maximum tolerated dose (MTD) of FT596 when given 30 days after transplant and
- 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 Design
Arms and Interventions
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:
|
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- Number of participants with relapse/progression [1 year post auto HSCT]
Number of participants experiencing progression or relapse at 12 months post auto HSCT
- Number of 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.
- Number of non-relapse mortality incidents at one year post HSCT [one year post auto-HSCT]
Number of participants experiencing non-relapse mortality at one year post auto-HSCT.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Minnesota | Minneapolis | Minnesota | United States | 55401 |
2 | Washington University School of Medicine - Siteman Cancer Center | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Masonic Cancer Center, University of Minnesota
Investigators
- Principal Investigator: Dr.Veronika Bachanova, MD, PhD, Masonic Cancer Center, University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2019LS230