Back to resultsFT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL
Primary Purpose
NHL, Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
FT596
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for NHL focused on measuring auto HSCT, Stem cell transplantation, Lymphoma
Eligibility 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.
Sites / Locations
- University of Minnesota
- Washington University School of Medicine - Siteman Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
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
Arm 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).
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).
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).
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Number of participants experiencing adverse events
Number of participants experiencing adverse events related to FT596 post auto-HSCT in combination with rituximab
Number of participants with relapse/progression
Number of participants experiencing progression or relapse at 12 months post auto HSCT
Number of non-relapse mortality incidents at 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
Number of participants experiencing non-relapse mortality at one year post auto-HSCT.
Full Information
NCT ID
NCT04555811
First Posted
September 14, 2020
Last Updated
February 21, 2023
Sponsor
Masonic Cancer Center, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT04555811
Brief Title
FT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL
Official Title
FATE FT596 With Rituximab as Relapse Prevention in High Risk Patients After Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 22, 2020 (Actual)
Primary Completion Date
February 8, 2023 (Actual)
Study Completion Date
February 2, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NHL, Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma
Keywords
auto HSCT, Stem cell transplantation, Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FT596 + Rituximab Dose Level 1: 9x10^7 cells/dose
Arm Type
Experimental
Arm 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).
Arm Title
FT596 + Rituximab Dose Level 2: 3x10^8 cells/dose
Arm Type
Experimental
Arm 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).
Arm Title
FT596 + Rituximab Dose Level 3: 9x10^8 cells/dose
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
FT596
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of participants experiencing dose limiting toxicity events
Description
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
Time Frame
28 Days Post FT596 infusion
Secondary Outcome Measure Information:
Title
Number of participants experiencing adverse events
Description
Number of participants experiencing adverse events related to FT596 post auto-HSCT in combination with rituximab
Time Frame
1 year post FT596 infusion
Title
Number of participants with relapse/progression
Description
Number of participants experiencing progression or relapse at 12 months post auto HSCT
Time Frame
1 year post auto HSCT
Title
Number of non-relapse mortality incidents at 100 days post HSCT
Description
Number of participants experiencing non-relapse mortality at 100 days post auto-HSCT.
Time Frame
100 days post HSCT
Title
Number of non-relapse mortality incidents at one year post HSCT
Description
Number of participants experiencing non-relapse mortality at one year post auto-HSCT.
Time Frame
one year post auto-HSCT
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr.Veronika Bachanova, MD, PhD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55401
Country
United States
Facility Name
Washington University School of Medicine - Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
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FT596 With Rituximab as Relapse Prevention After Autologous HSCT for NHL
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