Clinical trial NCT04555811: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: NHL
Non Hodgkin Lymphoma
Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
Keywords: auto HSCT
Stem cell transplantation
Lymphoma
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-09-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Experiencing Dose Limiting Toxicity Events
timeFrame: 28 Days Post FT596 infusion
Secondary outcomes:
measure: Number of Participants Experiencing Adverse Events
timeFrame: 1 year post FT596 infusion
measure: Percentage of Participants With Relapse/Progression
timeFrame: 1 year post auto HSCT
measure: Number of Participants Experiencing Non-relapse Mortality Incidents at 100 Days Post HSCT
timeFrame: 100 days post HSCT
measure: Percentage of Non-relapse Mortality Incidents at One Year Post HSCT
timeFrame: one year post auto-HSCT
measure: Progression-Free Survival 12 Months Post Auto-HCT
timeFrame: 12 Months Post Auto-HCT
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Dr.Veronika Bachanova, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: