FT596 as a Monotherapy and in Combination With Anti-CD20 Monoclonal Antibodies

Study Overview
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Brief Summary
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This is a Phase I dose-finding study of FT596 as monotherapy and in combination with Rituximab or Obinutuzumab in subjects with relapsed/refractory B-cell Lymphoma or Chronic Lymphocytic Leukemia. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Official Title
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A Phase I, Open-Label, Multicenter Study of FT596 as a Monotherapy and in Combination With Rituximab or Obinutuzumab in Subjects With Relapsed/Refractory B-cell Lymphoma and Chronic Lymphocytic Leukemia

Conditions
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Lymphoma, B-Cell, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: FT596
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Rituximab
* Drug: Obinutuzumab
* Drug: Bendamustine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of B-cell lymphoma or CLL as described below: B-Cell Lymphoma: Histologically documented lymphomas expected to express CD19 and CD20 Relapsed/refractory disease following prior systemic immunochemotherapy regimen Chronic Lymphocytic Leukemia (CLL): Diagnosis of CLL per iwCLL guidelines Relapsed/refractory disease following at least two prior systemic treatment regimens ALL SUBJECTS: Capable of giving signed informed consent Age ≥ 18 years old Stated willingness to comply with study procedures and duration Contraceptive use for women and men as defined in the protocol Key Exclusion Criteria: ALL SUBJECTS: Females who are pregnant or breastfeeding Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2 Body weight <50 kg Evidence of insufficient organ function Receipt therapy within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Day 1 Currently receiving or likely to require systemic immunosuppressive therapy Prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T within 6 months of Day 1, or ongoing requirement for systemic GvHD therapy Receipt of an allograft organ transplant Known active central nervous system (CNS) involvement by malignancy Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease Clinically significant cardiovascular disease Known HIV infection Known active Hepatitis B (HBV) or Hepatitis C (HCV) infection Live vaccine <6 weeks prior to start of lympho-conditioning Known allergy to albumin (human) or DMSO

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FT596 Monotherapy, Lymphoma<br>FT596 monotherapy in adult subjects with r/r B-cell Lymphoma | Drug: FT596<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>Drug: Bendamustine<br>* Conditioning agent<br>* Other names: Treanda;|
| Experimental: FT596 in Combination with Rituximab, Lymphoma<br>FT596 in combination with Rituximab in adult subjects with r/r B-cell Lymphoma | Drug: FT596<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>Drug: Rituximab<br>* Monoclonal Antibody<br>* Other names: Ruxience;Drug: Bendamustine<br>* Conditioning agent<br>* Other names: Treanda;|
| Experimental: FT596 in Combination with Obinutuzumab, Lymphoma<br>FT596 in combination with Obinutuzumab in adult subjects with r/r B-cell Lymphoma | Drug: FT596<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>Drug: Obinutuzumab<br>* Monoclonal Antibody<br>* Other names: Gazyva;Drug: Bendamustine<br>* Conditioning agent<br>* Other names: Treanda;|
| Experimental: FT596 Monotherapy, CLL<br>FT596 monotherapy in adult subjects with r/r CLL | Drug: FT596<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>Drug: Bendamustine<br>* Conditioning agent<br>* Other names: Treanda;|
| Experimental: FT596 in Combination with Obinutuzumab, CLL<br>FT596 in combination with Obinutuzumab in adult subjects with r/r CLL | Drug: FT596<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>Drug: Obinutuzumab<br>* Monoclonal Antibody<br>* Other names: Gazyva;Drug: Bendamustine<br>* Conditioning agent<br>* Other names: Treanda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities within each dose level cohort |  | Day 29 | 
| Nature of dose-limiting toxicities within each dose level cohort |  | Day 29 | 
| Incidence, nature, and severity of adverse events (AEs) of FT596 as monotherapy and in combination with rituximab or obinutuzumab in r/r B-cell lymphomas and r/r chronic lymphocytic leukemia, with severity determined according to NCI CTCAE, v5.0 |  | Up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed objective-response rate (ORR) | Proportion of subjects who achieve a partial response (PR) or complete response (CR) per Lugano 2014 classification for lymphomas, a partial remission (PR) or complete remission (CR) per revised iwCLL guidelines for CLL. | From baseline tumor assessment up to approximately 2 years after last dose of FT596 | 
| Investigator-assessed duration of objective response (DOR) | Defined as the duration from the first occurrence of a documented objective response (DOR) until the time of disease progression or relapse, or death from any cause, whichever occurs first, per Lugano 2014 classification for lymphomas or revised iwCLL guidelines for CLL. | Up to 15 years | 
| Investigator-assessed duration of complete response (DoCR) | Defined as the duration from the first occurrence of a documented complete response (CR) per Lugano 2014 classification for lymphomas or complete remission (CR) per revised iwCLL guidelines for CLL, until the time of disease progression or relapse, or death from any cause, whichever occurs first. | Up to 15 years | 
| Progression-free survival (PFS) | Defined as the time from from first dose of lympho-conditioning to progressive disease (PD), or to the day of death for any reason, whichever occurs earlier, based on Lugano 2014 classification for lymphomas or revised iwCLL guidelines for CLL | Up to 15 years | 
| Overall survival (OS), defined as the time from first dose of lympho-conditioning to death from any cause. |  | Up to 15 years | 
| The pharmacokinetics of FT596 in peripheral blood will be reported as the relative percentage of product (FT596) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points |  | Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Leukemia