FT819 in Subjects With B-cell Malignancies

Study Overview
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Brief Summary
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This is a Phase I dose-finding study of FT819 as monotherapy and in combination with IL-2 in subjects with relapsed/refractory B-cell Lymphoma, Chronic Lymphocytic Leukemia and Precursor B-cell Acute Lymphoblastic 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 Study of FT819 in Subjects With B-cell Malignancies

Conditions
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Lymphoma, B-Cell, Chronic Lymphocytic Leukemia, Precursor B-Cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: FT819
* 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 B-cell lymphoma, CLL or B-ALL as described below: B-Cell Lymphoma: Histologically documented lymphomas expected to express CD19 Relapsed/refractory disease following at least 2 prior lines of multi-agent immunochemotherapy Chronic Lymphocytic Leukemia (CLL): Diagnosis of CLL per iwCLL guidelines Relapsed/refractory disease following at least two prior systemic treatment regimens Precursor B-cell Acute Lymphocytic Leukemia (B-ALL): Diagnosis of B-ALL by flow cytometry, bone marrow histology, and/or cytogenetics Relapsed/refractory disease after at least 2 cycles of standard multiagent induction chemotherapy. For subjects with Philadelphia-chromosome positive (Ph+) disease, failure or intolerance to a tyrosine kinase inhibitor therapy-containing regimen 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 of 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 Ongoing requirement for systemic GvHD therapy following prior allogeneic hematopoietic stem cell transplant (HSCT) or allogeneic CAR-T 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 Positive serologic test results for HIV infection Positive serologic and polymerase chain reaction (PCR) test results for Hepatitis B (HBV) infection Positive serologic and PCR test results for 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: FT819 Single-Dose Monotherapy, B-Cell Lymphoma<br>FT819 single-dose monotherapy in adult subjects with r/r B-cell Lymphoma | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Single-Dose in Combination with IL-2, B-Cell Lymphoma<br>FT819 single-dose in combination with IL-2 in adult subjects with r/r B-cell Lymphoma | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: IL-2<br>* Biologic response modifier<br>* Other names: Interleukin-2;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Step Fractionated Monotherapy, B-Cell Lymphoma<br>FT819 monotherapy administered as step-fractionated dosing in adult subjects with r/r B-cell Lymphoma | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Single-Dose Monotherapy, CLL<br>FT819 single-dose monotherapy in adult subjects with r/r CLL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Single-Dose in Combination with IL-2, CLL<br>FT819 single-dose in combination with IL-2 in adult subjects with r/r CLL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: IL-2<br>* Biologic response modifier<br>* Other names: Interleukin-2;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Step Fractionated Monotherapy, CLL<br>FT819 monotherapy administered as step-fractionated dosing in adult subjects with r/r CLL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Single-Dose Monotherapy, B-ALL<br>FT819 single-dose monotherapy in adult subjects with r/r B-ALL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Single-Dose in Combination with IL-2, B-ALL<br>FT819 single-dose in combination with IL-2 in adult subjects with r/r B-ALL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: IL-2<br>* Biologic response modifier<br>* Other names: Interleukin-2;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Step Fractionated Monotherapy, B-ALL<br>FT819 monotherapy administered as step-fractionated dosing in adult subjects with r/r B-ALL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Step Fractionated Monotherapy in Combination with IL-2, B-Cell Lymphoma<br>FT819 monotherapy administered as step-fractionated dosing in combination with IL-2 in adult subjects with r/r B-cell Lymphoma | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: IL-2<br>* Biologic response modifier<br>* Other names: Interleukin-2;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Step Fractionated Monotherapy in Combination with IL-2, CLL<br>FT819 monotherapy administered as step-fractionated dosing in combination with IL-2 in adult subjects with r/r CLL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: IL-2<br>* Biologic response modifier<br>* Other names: Interleukin-2;Drug: Bendamustine<br>* Lympho-conditioning agent<br>* Other names: Treanda;|
| Experimental: FT819 Step Fractionated Monotherapy in Combination with IL-2, B-ALL<br>FT819 monotherapy administered as step-fractionated dosing in combination with IL-2 in adult subjects with r/r B-ALL | Drug: FT819<br>* Experimental Interventional Therapy<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>* Other names: Fludara;Drug: IL-2<br>* Biologic response modifier<br>* Other names: Interleukin-2;Drug: Bendamustine<br>* Lympho-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 and nature of dose-limiting toxicities within each dose level cohort |  | Up to Day 29 | 
| Incidence, nature, and severity of adverse events (AEs) of FT819 as monotherapy and in combination with IL-2 in r/r B-cell lymphoma, r/r chronic lymphocytic leukemia, and r/r precursor B-cell acute lymphoblastic leukemia |  | Up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed objective-response rate (ORR) |  | Up to approximately 2 years after last dose of FT819 | 
| For BCL and CLL Only: Investigator-assessed duration of objective response (DOR) |  | Up to 15 years | 
| For BCL and CLL Only: Investigator-assessed duration of complete response (DoCR) |  | Up to 15 years | 
| For BCL and CLL Only: Progression-free survival (PFS) |  | Up to 15 years | 
| Overall survival (OS) |  | Up to 15 years | 
| Determination of the pharmacokinetics of FT819 cells in peripheral blood. | The PK of FT819 in peripheral blood will be reported as the relative percentage of product (FT819) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points | Study Days 1, 2, 3, 4, 5, 8, 11, 15, 22, and 29 | 
| For B-ALL Only: Investigator-assessed relapse-free survival (RFS) |  | Up to 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Leukemia, BCL, CLL, B-ALL, CAR-T, cellular therapy