Evaluation of Lymphodepletion With ALLO-647 in Adults With R/R Large B Cell Lymphoma Receiving ALLO-501A Allogeneic CAR T Cell Therapy

Study Overview
=================
Brief Summary
-----------------
The purpose of the EXPAND study is to assess the safety and clinical efficacy of ALLO-647 combined with fludarabine and cyclophosphamide compared to fludarabine and cyclophosphamide alone in a lymphodepletion regimen prior to ALLO-501A CAR T therapy in adults with relapsed or refractory large B-cell lymphoma

Official Title
-----------------
A Randomized, Open-Label, Phase 2 Study Evaluating Lymphodepletion With ALLO-647, Fludarabine, and Cyclophosphamide, vs. Fludarabine and Cyclophosphamide Alone, in Subjects With Relapsed/Refractory Large B-Cell Lymphoma Receiving ALLO-501A Allogeneic CAR T Cell Therapy

Conditions
-----------------
Relapsed/Refractory Large B Cell Lymphoma

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse Relapsed or refractory disease after at least 2 lines of chemotherapy ECOG performance status 0 or 1 Absence of significant donor (product)-specific anti-HLA antibodies (DSA) Adequate hematological, renal and liver function Exclusion Criteria: Active central nervous system involvement by malignancy Autologous or allogeneic HSCT within last 6 months prior to lymphodepletion Hypocellular bone marrow for age

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lymphodepletion with ALLO-647, fludarabine, and cyclophosphamide<br>ALLO-501A CAR T cells infused following lymphodepletion | 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>Genetic: ALLO-501A<br>* ALLO-501A is an allogeneic CAR T cell therapy targeting CD19<br>|
| Experimental: Lymphodepletion with fludarabine and cyclophosphamide<br>ALLO-501A CAR T cells infused following lymphodepletion | Drug: Fludarabine<br>* Chemotherapy for lymphodepletion<br>Drug: Cyclophosphamide<br>* Chemotherapy for lymphodepletion<br>Genetic: ALLO-501A<br>* ALLO-501A is an allogeneic CAR T cell therapy targeting CD19<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the clinical efficacy of ALLO-647 (in a lymphodepletion regimen before ALLO-501A) compared to FC alone as measured by PFS and assessed by IRC in subjects with R/R (Relapsed / Refractory) LBCL (Large B Cell Lymphoma) |  | Up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the clinical efficacy of ALLO-647 as measured by Overall Response Rate (ORR) and assessed by IRC between treatment arms |  | Up to 60 months | 
| To assess clinical efficacy of ALLO-647 with FC (in a lymphodepletion regimen before ALLO-501A) compared to FC alone as measured by Event-Free Survival (EFS) and assessed by IRC in subjects with R/R LBCL |  | Up to 60 months | 
| To characterize the efficacy of ALLO-647 as measured by Duration of Response (DOR) and assessed by IRC between treatment arms |  | Up to 60 months | 
| To characterize the efficacy of ALLO-647 as measured by Progression Free Survival (PFS) and assessed by IRC between treatment arms |  | Up to 60 months | 
| To characterize the efficacy of ALLO-647 as measured by response rate per investigator review |  | Up to 60 months | 
| To characterize the efficacy of ALLO-647 as measured by DOR and assessed by investigator assessments between treatment arms |  | Up to 60 months | 
| To characterize the efficacy of ALLO-647 as measured by Overall Survival (OS) |  | Up to 60 months | 
| To characterize lymphodepletion with and without ALLO-647 as measured by absolute lymphocyte count/microliter; T cell counts/microliter; B cell counts/microliter, NK cell counts/microliter |  | Up to 9 months | 
| To characterize the serum concentration of ALLO-647 as measured by microgram per microliter |  | Up to 10 days | 
| To characterize blood concentration of ALLO-501A when administered with lymphodepletion with and without ALLO-647 as measured by vector copy number |  | Up to 9 months | 
| To characterize the effects of ALLO-647 on host T cell concentrations as measured by T cell counts cells/microliter |  | Up to 9 months | 
| To evaluate the rate of anti-drug antibodies against ALLO-647 and ALLO-501A |  | Up to 9 months | 
| To evaluate the incidence of treatment-emergent adverse events of ALLO-647 by comparing ALLO-647, fludarabine, and cyclophosphamide (FCA) lymphodepletion with fludarabine and cyclophosphamide (FC) lymphodepletion |  | Up to 60 months | 
| To evaluate the incidence of treatment-emergent adverse events of ALLO-501A following lymphodepletion |  | Up to 60 months | 

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