FT516 in Subjects With Advanced Hematologic Malignancies

Study Overview
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Brief Summary
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This is a Phase 1/1b dose-finding study of FT516 as monotherapy in acute myeloid leukemia (AML) and in combination with CD20 directed monoclonal antibodies in B-cell lymphoma. The study includes three stages: dose escalation, safety confirmation, and dose expansion.

Official Title
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A Phase I Study of FT516 as Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination With Monoclonal Antibodies in Relapsed/Refractory B-Cell Lymphoma

Conditions
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Acute Myelogenous Leukemia, B-cell Lymphoma

Intervention / Treatment
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* Drug: FT516
* Drug: Rituximab
* Drug: Obinutuzumab
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: IL-2
* Drug: Bendamustine


Participation Criteria
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Eligibility Criteria
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KEY INCLUSION CRITERIA: Diagnosis of the following: Regimen A (FT516 monotherapy): Primary Refractory AML Relapsed AML defined as not in CR after 1 or more re-induction attempts; if >60 years of age, prior re-induction therapy is not required Regimen B (FT516 + rituximab or obinutuzumab): Histologically documented B-cell lymphoma expected to express CD20 who have relapsed after or failed to respond to at least on prior treatment regimen and for whom there is no available therapy expected to improve survival. All subjects: Provision of signed and dated informed consent form (ICF) Age ≥18 years old Stated willingness to comply with study procedures and duration Presence of measurable disease KEY EXCLUSION CRITERIA: All subjects: Females of reproductive potential who are pregnant or lactating, and males or females not willing to use a highly effective form of contraception from Screening through the end of the study Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2 Evidence of insufficient organ function Receipt of therapy within 2 weeks prior to Cycle 1 Day 1 or within five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to Cycle 1 Day 1 Currently receiving or likely to require systemic immunosuppressive therapy Prior allogeneic HSCT or allogeneic CAR-T within 6 months of Cycle 1 Day 1, or ongoing requirement for systemic graft-versus-host therapy Receipt of an allograft organ transplant Known active central nervous system (CNS) involvement by malignancy. Clinically significant cardiovascular disease Clinically significant infections including: 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 human albumin and DMSO Additional Exclusion Criteria for FT516 monotherapy Regimen: Diagnosis of promyelocytic leukemia with t(15:17) translocation Additional Exclusion Criteria for FT516 plus monoclonal antibody Regimens: Diagnosis of Waldenstrom macroglobulinemia

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FT516 Monotherapy<br>FT516 monotherapy in adult subjects with r/r AML. | Drug: FT516<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Conditioning agent<br>Drug: Fludarabine<br>* Conditioning agent<br>Drug: IL-2<br>* Biologic response modifier<br>|
| Experimental: FT516 in Combination with Monoclonal Antibodies<br>FT516 in combination with one of the following monoclonal antibodies in adult subjects with r/r B-cell lymphoma: rituximab or obinutuzumab. | Drug: FT516<br>* Experimental Interventional Therapy<br>Drug: Rituximab<br>* Monoclonal Antibody<br>* Other names: MabThera;Drug: Obinutuzumab<br>* Monoclonal Antibody<br>* Other names: Gazyva;Drug: Cyclophosphamide<br>* Conditioning agent<br>Drug: Fludarabine<br>* Conditioning agent<br>Drug: IL-2<br>* Biologic response modifier<br>|
| Experimental: FT516 in Combination with Monoclonal Antibodies on an Extended-Dosing Schedule<br>FT516 on an extended-dosing schedule in combination with one of the following monoclonal antibodies in adult subjects with r/r B-cell lymphoma: rituximab or obinutuzumab. | Drug: FT516<br>* Experimental Interventional Therapy<br>Drug: Rituximab<br>* Monoclonal Antibody<br>* Other names: MabThera;Drug: Obinutuzumab<br>* Monoclonal Antibody<br>* Other names: Gazyva;Drug: Cyclophosphamide<br>* Conditioning agent<br>Drug: Fludarabine<br>* Conditioning agent<br>Drug: IL-2<br>* Biologic response modifier<br>|
| Experimental: FT516 in Combination with Monoclonal Antibodies following Bendamustine Conditioning<br>Bendamustine conditioning followed by FT516 in combination with one of the following monoclonal antibodies in adult subjects with r/r B-cell lymphoma: rituximab or obinutuzumab. | Drug: FT516<br>* Experimental Interventional Therapy<br>Drug: Rituximab<br>* Monoclonal Antibody<br>* Other names: MabThera;Drug: Obinutuzumab<br>* Monoclonal Antibody<br>* Other names: Gazyva;Drug: IL-2<br>* Biologic response modifier<br>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 |
| --- | --- | --- |
| The incidence of subjects with Dose Limiting Toxicities within each dose level cohort. |  | Day 29 | 
| Incidence, nature, and severity of AEs, of FT516 as monotherapy in r/r AML and in combination with rituximab or obinutuzumab in r/r B-cell lymphoma. |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed anti-tumor activity of FT516 as monotherapy in r/r AML and in combination with rituximab or obinutuzumab in r/r B-cell lymphoma. |  | Cycle 2 Day 29 | 
| FT516 pharmacokinetic data | Percentage of donor DNA measured at each timepoint | Cycle 1 and Cycle 2 Study Days: 1, 2, 4, 8, 11, 15, 18, 22, 29, and Cycle 2 Day 43 and Cycle 2 Day 57. | 

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