Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, NHL, Non Hodgkin Lymphoma
Conditions
Keywords
auto HSCT, Stem cell transplantation, Lymphoma
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.
Interventions
DRUGFT596
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.
DRUGRituximab
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
Sponsors
National Cancer Institute (NCI)
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Percentage of Participants With Relapse/Progression | 1 year post auto HSCT | Percentage of participants experiencing progression or relapse at 12 months post auto HSCT |
| Number of Participants Experiencing 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. |
| Percentage of Non-relapse Mortality Incidents at One Year Post HSCT | one year post auto-HSCT | Percentage of participants experiencing non-relapse mortality at one year post auto-HSCT. |
| Progression-Free Survival 12 Months Post Auto-HCT | 12 Months Post Auto-HCT | Progression-Free Survival 12 Months Post Auto-HCT |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
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.
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 | 3 |
| 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).
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.
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 | 3 |
| 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).
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.
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 | 1 |
| Total | 7 |
Baseline characteristics
| Characteristic | FT596 + Rituximab Dose Level 2: 3x10^8 Cells/Dose | FT596 + Rituximab Dose Level 3: 9x10^8 Cells/Dose | Total | FT596 + Rituximab Dose Level 1: 9x10^7 Cells/Dose |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 5 Participants | 2 Participants |
| Region of Enrollment United States | 3 participants | 1 participants | 7 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 3 / 3 | 1 / 1 |
| other Total, other adverse events | 3 / 3 | 0 / 3 | 1 / 1 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 1 |
Outcome results
Primary
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
Time frame: 28 Days Post FT596 infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FT596 + Rituximab Dose Level 1: 9x10^7 Cells/Dose | Number of Participants Experiencing Dose Limiting Toxicity Events | 0 Participants |
| FT596 + Rituximab Dose Level 2: 3x10^8 Cells/Dose | Number of Participants Experiencing Dose Limiting Toxicity Events | 0 Participants |
| FT596 + Rituximab Dose Level 3: 9x10^8 Cells/Dose | Number of Participants Experiencing Dose Limiting Toxicity Events | 0 Participants |
Secondary
Number of Participants Experiencing Adverse Events
Number of participants experiencing adverse events related to FT596 post auto-HSCT in combination with rituximab
Time frame: 1 year post FT596 infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FT596 + Rituximab Dose Level 1: 9x10^7 Cells/Dose | Number of Participants Experiencing Adverse Events | 3 participants |
| FT596 + Rituximab Dose Level 2: 3x10^8 Cells/Dose | Number of Participants Experiencing Adverse Events | 0 participants |
| FT596 + Rituximab Dose Level 3: 9x10^8 Cells/Dose | Number of Participants Experiencing Adverse Events | 1 participants |
Secondary
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.
Time frame: 100 days post HSCT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FT596 + Rituximab Dose Level 1: 9x10^7 Cells/Dose | Number of Participants Experiencing Non-relapse Mortality Incidents at 100 Days Post HSCT | 0 Participants |
| FT596 + Rituximab Dose Level 2: 3x10^8 Cells/Dose | Number of Participants Experiencing Non-relapse Mortality Incidents at 100 Days Post HSCT | 0 Participants |
| FT596 + Rituximab Dose Level 3: 9x10^8 Cells/Dose | Number of Participants Experiencing Non-relapse Mortality Incidents at 100 Days Post HSCT | 0 Participants |
Secondary
Percentage of Non-relapse Mortality Incidents at One Year Post HSCT
Percentage of participants experiencing non-relapse mortality at one year post auto-HSCT.
Time frame: one year post auto-HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FT596 + Rituximab Dose Level 1: 9x10^7 Cells/Dose | Percentage of Non-relapse Mortality Incidents at One Year Post HSCT | 67 Percentage of participants |
| FT596 + Rituximab Dose Level 2: 3x10^8 Cells/Dose | Percentage of Non-relapse Mortality Incidents at One Year Post HSCT | 100 Percentage of participants |
| FT596 + Rituximab Dose Level 3: 9x10^8 Cells/Dose | Percentage of Non-relapse Mortality Incidents at One Year Post HSCT | 100 Percentage of participants |
Secondary
Percentage of Participants With Relapse/Progression
Percentage of participants experiencing progression or relapse at 12 months post auto HSCT
Time frame: 1 year post auto HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FT596 + Rituximab Dose Level 1: 9x10^7 Cells/Dose | Percentage of Participants With Relapse/Progression | 67 Percentage of participants |
| FT596 + Rituximab Dose Level 2: 3x10^8 Cells/Dose | Percentage of Participants With Relapse/Progression | 33 Percentage of participants |
| FT596 + Rituximab Dose Level 3: 9x10^8 Cells/Dose | Percentage of Participants With Relapse/Progression | 0 Percentage of participants |
Secondary
Progression-Free Survival 12 Months Post Auto-HCT
Progression-Free Survival 12 Months Post Auto-HCT
Time frame: 12 Months Post Auto-HCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FT596 + Rituximab Dose Level 1: 9x10^7 Cells/Dose | Progression-Free Survival 12 Months Post Auto-HCT | 33 Percentage of participants |
| FT596 + Rituximab Dose Level 2: 3x10^8 Cells/Dose | Progression-Free Survival 12 Months Post Auto-HCT | 67 Percentage of participants |
| FT596 + Rituximab Dose Level 3: 9x10^8 Cells/Dose | Progression-Free Survival 12 Months Post Auto-HCT | 100 Percentage of participants |