Safety and Efficacy of ALLO-501 Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell or Follicular Lymphoma

Study Overview
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Brief Summary
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The purpose of the ALPHA study is to assess the safety, efficacy, cell kinetics and immunogenicity of ALLO-501 in adults with relapsed or refractory large B-cell lymphoma or follicular lymphoma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.

Official Title
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A Single-Arm, Open-Label, Phase 1 Study Evaluating the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-501, an Anti-CD19 Allogeneic CAR T Cell Therapy, And ALLO-647, An Anti-CD52 Monoclonal Antibody, in Patients With Relapsed/Refractory Large B-Cell Lymphoma or Follicular Lymphoma

Conditions
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Relapsed/Refractory Large B Cell Lymphoma, Relapsed/Refractory Follicular Lymphoma

Intervention / Treatment
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* Genetic: ALLO-501
* Biological: ALLO-647
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of Large B-cell Lymphoma (LBCL) or Follicular Lymphoma. Relapse or refractory disease after at least 2 lines of chemotherapy At least 1 measurable lesion at time of screening. Eastern Cooperative Oncology Group Performance Status of 0 or 1. Adequate hematological, renal, liver, pulmonary, and cardiac functions. Exclusion Criteria: Current or history of central nervous system (CNS) lymphoma. Clinically significant CNS dysfunction. ASCT within last 6 weeks or allogeneic HSCT within last 3 months prior to ALLO-647. Prior treatment with anti-CD19 therapy, any gene therapy, any genetically modified cell therapy or adoptive T cell therapy Systemic anticancer therapy within 2 weeks prior to study entry. On-going treatment with immunosuppressive agents. Active acute or chronic graft versus host disease (GvHD), or GvHD requiring immunosuppressive treatment within 4 weeks of enrollment. Any form of primary or acquired immunodeficiency (e.g., severe combined immunodeficiency disease). Current thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy. Patients unwilling to participate in an extended safety monitoring period

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALLO-647, ALLO-501<br> | Genetic: ALLO-501<br>* ALLO-501 is an allogeneic CAR T cell therapy targeting CD19<br>Biological: ALLO-647<br>* ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen<br>Drug: Fludarabine<br>* Chemotherapy for lymphodepletion<br>Drug: Cyclophosphamide<br>* Chemotherapy for lymphodepletion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-501 | Dose limiting toxicity is defined as protocol-defined ALLO-501-related adverse events with onset within 28 days following infusion | 28 days | 
| Proportion of patients experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501 | Dose-limiting toxicity is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion | 33 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T, Cell Therapy, Allogeneic Cell Therapy, Cellular Immuno-therapy, AlloCAR T, ALLO-501, ALLO-647, LBCL, Lymphoma, Follicular Lymphoma, Large B-Cell Lymphoma