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

Sponsor

Allogene Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05714345

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Large B Cell Lymphoma	Biological: ALLO-647 Drug: Fludarabine Drug: Cyclophosphamide Genetic: ALLO-501A	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Sep 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lymphodepletion with ALLO-647, fludarabine, and cyclophosphamide ALLO-501A CAR T cells infused following lymphodepletion	Biological: ALLO-647 ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen Drug: Fludarabine Chemotherapy for lymphodepletion Drug: Cyclophosphamide Chemotherapy for lymphodepletion Genetic: ALLO-501A ALLO-501A is an allogeneic CAR T cell therapy targeting CD19
Experimental: Lymphodepletion with fludarabine and cyclophosphamide ALLO-501A CAR T cells infused following lymphodepletion	Drug: Fludarabine Chemotherapy for lymphodepletion Drug: Cyclophosphamide Chemotherapy for lymphodepletion Genetic: ALLO-501A ALLO-501A is an allogeneic CAR T cell therapy targeting CD19

Arm

Intervention/Treatment

Experimental: Lymphodepletion with ALLO-647, fludarabine, and cyclophosphamide

ALLO-501A CAR T cells infused following lymphodepletion

Biological: ALLO-647

ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen

Drug: Fludarabine

Chemotherapy for lymphodepletion

Drug: Cyclophosphamide

Chemotherapy for lymphodepletion

Genetic: ALLO-501A

ALLO-501A is an allogeneic CAR T cell therapy targeting CD19

Experimental: Lymphodepletion with fludarabine and cyclophosphamide

ALLO-501A CAR T cells infused following lymphodepletion

Drug: Fludarabine

Chemotherapy for lymphodepletion

Drug: Cyclophosphamide

Chemotherapy for lymphodepletion

Genetic: ALLO-501A

ALLO-501A is an allogeneic CAR T cell therapy targeting CD19

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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