A Study Evaluating the Safety and Efficacy of BEAM-201 in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LL)

Study Overview
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Brief Summary
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This is a Phase 1/2, multicenter, open-label study to evaluate the safety and efficacy of BEAM-201 in patients with relapsed/refractory T-ALL or T-LL. This study consists of Phase 1 dose-exploration cohorts, Phase 1 dose-expansion cohort(s), a Phase 1 pediatric cohort (will enroll patients ages 1 to < 12 years), and a Phase 2 cohort.

Official Title
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A Phase 1/2, Dose-Exploration and Dose-Expansion Study Evaluating the Safety and Efficacy of Multiplex Base-Edited, Allogeneic Anti-CD7 CAR-T Cells (BEAM-201) in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LL)

Conditions
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T-Cell Lymphoblastic Leukemia/Lymphoma, Lymphoblastic Leukemia, Lymphoblastic Lymphoma

Intervention / Treatment
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* Biological: BEAM-201


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Ages 18 to ≤ 50 years. Ages ≥ 1 year to < 18 years, after health authority approval. T-ALL/T-LL that is CD7-positive (defined as at least 20% of blasts positive for CD7 by flow cytometry or immunohistochemistry based on assessment of the study site's CLIA [Clinical Laboratory Improvement Amendments of 1988] certified facility) in second or greater relapse, first relapse post-transplant relapse, or chemotherapy-refractory disease. Specifically: Second or greater relapse or post-transplant relapse, defined as: BM with ≥ 5% lymphoblasts by morphologic assessment or evidence of extramedullary disease at screening after second documented CR; OR Flow cytometric confirmation of relapsed T-ALL of at least 0.1% after second CR documented to have been MRD negative < 0.1%; OR Any detectable relapsed disease post-allogeneic HSCT with flow cytometric confirmation of T-ALL of at least 0.1%; OR Biopsy confirmed evidence of relapsed T-LL on lymph node biopsy after second CR; OR Any detectable disease post-allogeneic transplant with biopsy confirmed evidence of T-LL on lymph node biopsy Refractory disease, defined as: Primary refractory T-ALL or T-LL, defined as failure to achieve CR after induction chemotherapy, per investigator assessment and based on biopsy-confirmed evidence of residual T-ALL or T-LL; OR Relapsed, refractory disease, defined as > 5% BM blasts or biopsy-confirmed evidence of residual TLL after 1 course of re-induction chemotherapy for patients who have relapsed after previously achieving a CR NOTE: Patients with mixed phenotype acute leukemia with T-cell dominant phenotype may be enrolled if the aforementioned criteria are met. Eligible for myeloablative conditioning for and allogeneic HSCT based on the investigator's assessment with an available donor identified by a FACT accredited transplant center. Key Exclusion Criteria: CNS involvement meeting any of the following criteria: CNS-3 disease, progressive CNS involvement despite therapy, CNS parenchymal or cranial nerve lesions on imaging. Clinically active CNS dysfunction or known history of irreversible neurological toxicity related to prior antileukemic therapy. Receipt of prior CD7 targeted therapy. Systemic antileukemic therapy intended to induce or maintain remission within 14 days prior to completion of screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Interventional Model Description: The maximum number of patients for this study is approximately 102 patients: 36 patients in the Phase 1 dose exploration approximately 12 patients in the Phase 1 dose-expansion cohorts 6 patients in the pediatric cohort approximately 48 patients in the Phase 2 cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fludarabine, cyclophosphamide and alemtuzumab<br>Lymphodepletion regimen including fludarabine, cyclophosphamide and alemtuzumab | Biological: BEAM-201<br>* A single dose of BEAM-201 administered by IV following one of two lymphodepletion regimens<br>|
| Experimental: Fludarabine, cyclophosphamide without alemtuzumab<br>Lymphodepletion regimen without Alz but consisting of the same dose of Flu/Cy as in the other arm | Biological: BEAM-201<br>* A single dose of BEAM-201 administered by IV following one of two lymphodepletion regimens<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-related adverse events, including serious adverse events (SAEs) and dose-limiting toxicities (DLTs; in Phase 1 only) |  | Through study completion, an average of 25 months | 
| Overall response rate as defined as proportion of T-ALL patients achieving complete response (CR) or complete response with incomplete hematologic recovery (CRi) or T-LL patients achieving CR or PR at any point after BEAM-201 infusion |  | From treatment with BEAM-201 through study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve MRD negative response (defined as < 0.1%) by flow cytometry or next generation sequencing (NGS) in patients achieving morphologic response |  | Starting at Day 28 and multiple time points up to Month 24 | 
| Proportion of patients treated with BEAM-201 deemed appropriate for HSCT based on investigator assessment of clinical response |  | Through study completion, an average of 25 months | 
| Duration of Response (DOR) |  | Through study completion, an average of 25 months | 
| Relapse-free survival (RFS) |  | Through study completion, an average of 25 months | 
| Overall survival |  | Through study completion, an average of 25 months | 
| Relapse-related mortality |  | Through study completion, an average of 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Base editing, CAR-T