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

Phase 2TerminatedNCT05714345

Allogene Therapeutics2 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Relapsed/Refractory Large B Cell Lymphoma

Interventions

ALLO-647BIOLOGICAL

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

FludarabineDRUG

Chemotherapy for lymphodepletion

CyclophosphamideDRUG

Chemotherapy for lymphodepletion

ALLO-501A

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, United States

Universitair Ziekenhuis Brussel

Brussels, Belgium

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) of a Lymphodepletion Regimen Containing FCA vs FC Alone Per Independent Review Committee

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 Independent Review Committee (IRC) in subjects with R/R (Relapsed / Refractory) LBCL (Large B Cell Lymphoma). In this study, PFS is defined as the time from randomization to disease progression, or relapse per the Lugano classification criteria (Cheson et al, 2014) as assessed by IRC or death.

Time frame: Up to 60 months

Secondary Outcomes

Overall-response Rate (ORR) of a Lymphodepletion Regimen Containing FCA vs FC Per Independent Review Committee

To assess the clinical efficacy of ALLO-647 as measured by ORR and assessed by Independent Review Committee (IRC) between treatment arms. ORR is defined as best overall response (Complete Response and Partial Response, assessed using the Lugano classification criteria 2014; Cheson , et al, 2014) by IRC at any time up through commencement of new anti-cancer therapy or withdrawal of consent.

Time frame: Up to 60 months

Event-Free-Survival (EFS) of a Lymphodepletion Regimen Containing FCA vs FC Per Independent Review Committee

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 Independent Review Committee (IRC) in subjects with R/R LBCL. EFS is defined as the time from randomization to disease progression or relapse per the Lugano classification criteria 2014 as assessed by IRC, new anti-cancer therapy, or death.

Time frame: Up to 60 months

Duration of Response (DOR) of a Lymphodepletion Regimen Containing FCA vs FC Per Independent Review Committee

To characterize the efficacy of ALLO-647 as measured by Duration of Response (DOR) and assessed by Independent Review Committee (IRC) between treatment arms. DOR is defined as time from the first observed response to disease progression or relapse (per IRC) or death.

Data from ClinicalTrials.gov

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

Time frame: Up to 60 months

Overall Survival (OS) of a Lymphodepletion Regimen Containing FCA vs FC

To characterize the efficacy of ALLO-647 as measured by OS, defined as the time from randomization to death.

Time frame: Up to 60 months, study completion, or death, whichever occurs earlier. Specifically, OS was followed for 4.5 and 10.09 months for each participant in the FCA and FC arm, respectively.

Duration of Response, Event-Free Survival and Progression-Free Survival of a Lymphodepletion Regimen Containing FCA vs FC Based on Response Assessment Per Investigator Review

To characterize the efficacy of ALLO-647 as measured by response rate per investigator, Duration of Response (DOR), Event-Free Survival (EFS), Progression-Free Survival (PFS), assessed by investigator assessments between treatment arms. DOR is defined as time from the first observed response to disease progression or relapse per investigator assessment, or death. EFS is defined as the time from randomization to disease progression or relapse per investigator assessment per the Lugano classification criteria, new anti-cancer therapy, or death. PFS is defined as time from the randomization to progression or relapse per investigator assessment per the Lugano classification criteria, or death.

Time frame: Neither participant was a responder, therefore DOR was not followed. EFS and PFS were followed from first dose of study treatment until disease progression, subsequent anticancer therapy, or death. EFS and PFS were followed for 0.99 to 1.84 months.

Overall Response Rate of a Lymphodepletion Regimen Containing FCA vs FC Based on Response Assessment Per Investigator Review

To characterize the efficacy of ALLO-647 as measured by response rate per investigator, Overall Response Rate (ORR), and assessed by investigator assessments between treatment arms. ORR in FCA vs FC alone per investigator assessment at any time up through commencement of new anti-cancer therapy or withdrawal of consent.

Time frame: Overall Response Rate was followed until disease progression or subsequent anticancer therapy, whichever occurred earlier. Specifically, ORR was followed for 0.99 to 1.84 months for each participant in the FCA and FC arm, respectively.

Depth and Duration of a Lymphodepletion Regimen Containing FCA vs FC

To characterize the depth and duration of lymphodepletion with and without ALLO-647, as assessed by lymphocyte count.

Time frame: From study treatment to study discontinuation, death, withdrawal of consent, or date of initiation of another anticancer therapy, whichever occurs first, for a maximum of 9 months. Only Day 28 lymphocyte counts are available for both participants.

Incidence of Treatment-Emergent Adverse Events (TEAEs)

To evaluate the overall safety profile of ALLO-647 by comparing FCA lymphodepletion with FC lymphodepletion.

Time frame: Up to 60 months, study completion, or death, whichever occurs earlier. TEAEs were followed for 4.5 and 10.09 months for each participant in the FCA and FC arm, respectively.

Incidence of ALLO-501A Related Treatment Emergent Adverse Events

To evaluate the overall safety profile of ALLO-501A following lymphodepletion.

Time frame: Up to 60 months, study completion, or death, whichever occurs earlier. Related TEAEs were followed for 4.5 and 10.09 months for each participant in the FCA and FC arm, respectively.