Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma (ALPHA2) (ALPHA2)

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ClinicalTrials.gov Identifier: NCT04416984

Recruitment Status : Recruiting

First Posted : June 4, 2020

Last Update Posted : February 9, 2023

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Allogene Therapeutics

Tracking Information

First Submitted Date ^ICMJE

May 29, 2020

First Posted Date ^ICMJE

June 4, 2020

Last Update Posted Date

February 9, 2023

Actual Study Start Date ^ICMJE

May 21, 2020

Estimated Primary Completion Date

January 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Phase 1: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A [ Time Frame: 28 days ]
Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion
Phase 1: Proportion of patients experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A [ Time Frame: 33 days ]
DLT is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion
Phase 2: Overall Response Rate (ORR) assessed per Independent Review Committee (IRC) [ Time Frame: Up to 60 months ]
ORR defined as assessment of CR and PR using Lugano classification criteria 2014

Original Primary Outcome Measures ^ICMJE

Phase 1: Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-501A [ Time Frame: 28 days ]
Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion
Phase 1: Proportion of patients experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A [ Time Frame: 33 days ]
Dose-limiting toxicity is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion
Phase 2: Overall Response Rate [ Time Frame: up to 13 months ]
Overall response rate assessed by independent radiology review

Change History

Current Secondary Outcome Measures ^ICMJE

Phase 1 and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator [ Time Frame: Up to 60 months ]
DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression or death, whichever comes first per (Cheson et al, 2014)
Phase 1 and 2: Overall Response Rate (ORR) assessed per investigator [ Time Frame: Up to 60 months ]
Phase 1 and 2: Best overall response (CR, PR, SD, PD) assessed per IRC (Phase 2 only) and per investigator [ Time Frame: Up to 60 months ]
CR Complete Response, PR Partial Response, SD Stable Disease, PD Progressive Disease
Phase 1 and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator [ Time Frame: Up to 60 months ]
PFS, defined as time from the enrollment date to progression, relapse, or death
Phase 1 and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator [ Time Frame: Up to 60 months ]
TTR, defined as the time from the enrollment date to the first observed response
Phase 1 and 2: Overall Survival (OS) [ Time Frame: Up to 60 months ]
OS, defined as the time from the enrollment date to death
Phase 1 and 2: Depth of lymphodepletion as assessed by lymphocyte count [ Time Frame: Up to 9 months ]
Phase 1 and 2: Duration of lymphodepletion as assessed by lymphocyte recovery [ Time Frame: Up to 9 months ]
Phase 1 and 2: Serum concentration of ALLO-647 as measured by microgram per microliter for use in a population PK model [ Time Frame: Up to 9 months ]
Phase 1 and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax) [ Time Frame: Up to 9 months ]
Phase 1 and 2: ALLO-501A expansion assessed by area under the curve (AUC) [ Time Frame: Up to 9 months ]
Phase 1 and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax) [ Time Frame: Up to 9 months ]
Phase 1 and 2: ALLO-501A persistence assessed by area under the curve (AUC) [ Time Frame: Up to 9 months ]
Phase 1 and 2: Pharmacodynamics will be evaluated on host T cell counts [ Time Frame: Up to 9 months ]
Phase 1 and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN® [ Time Frame: Up to 9 months ]
Phase 1 and 2: The incidence of anti-drug antibodies against ALLO-647 [ Time Frame: Up to 9 months ]
Phase 1 and 2: Adverse Events (AEs) as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A [ Time Frame: Up to 60 months ]
The incidence and severity of Cytokine Release Syndrome (CRS), Graft-Versus-Host Disease (GVHD), infections, cytopenias, and neurotoxicity
Phase 1 and 2: AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647 [ Time Frame: Up to 60 months ]
The incidence of infusion-related reactions, cytopenias, and infections
Phase 1 and 2: The incidence and severity of clinically significant laboratory toxicities [ Time Frame: Up to 60 months ]

Original Secondary Outcome Measures ^ICMJE

Phase 1 and 2: Incidence and severity of adverse events with ALLO-501A and ALLO-647 in combination with fludarabine/cyclophosphamide [ Time Frame: up to 13 months ]
Phase 1 and 2: Cellular kinetics of ALLO-501A in target tissues [ Time Frame: up to 13 months ]
Levels of Anti-CD19 CAR T cells in blood
Phase 1 and 2: Pharmacokinetics of ALLO-647 [ Time Frame: up to 13 months ]
Serum concentration levels of ALLO-647
Phase 1 and 2: Immunogenicity against ALLO-501A and ALLO-647 [ Time Frame: up to 13 months ]
Detection of antibodies in blood against ALLO-501A and ALLO-647
Phase 1 and 2: Immune monitoring after lymphodepletion regimen [ Time Frame: up to 13 months ]
Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells
Phase 2: Overall response rate [ Time Frame: up to 13 months ]
Overall response rate per investigator assessment
Phase 2: Time to response [ Time Frame: up to 13 months ]
Phase 2: Duration of Response [ Time Frame: up to 13 months ]
Phase 2: Progression free survival [ Time Frame: up to 13 months ]
Phase 2: Overall survival [ Time Frame: up to 13 months ]

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma (ALPHA2)

Official Title ^ICMJE

A Single-Arm, Open-Label, Phase 1/2 Study Evaluating the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-501A, an Anti-CD19 Allogeneic CAR T Cell Therapy, and ALLO-647, an Anti-CD52 Monoclonal Antibody, in Subjects With Relapsed/Refractory Large B-Cell Lymphoma (LBCL)

Brief Summary

The purpose of the ALPHA-2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Relapsed/Refractory Large B Cell Lymphoma

Intervention ^ICMJE

Genetic: ALLO-501A
ALLO-501A is an allogeneic CAR T cell therapy targeting CD19
Biological: ALLO-647
ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen
Drug: Fludarabine
Chemotherapy for lymphodepletion
Drug: Cyclophosphamide
Chemotherapy for lymphodepletion

Study Arms ^ICMJE

Experimental: ALLO-501A, ALLO-647

Interventions:

Genetic: ALLO-501A
Biological: ALLO-647
Drug: Fludarabine
Drug: Cyclophosphamide

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

160

Original Estimated Enrollment ^ICMJE

120

Estimated Study Completion Date ^ICMJE

May 2029

Estimated Primary Completion Date

January 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017
At least 1 measurable lesion at time of enrollment
Relapsed or refractory disease after at least 2 lines of chemotherapy
ECOG performance status 0 or 1
Absence of donor (product)-specific anti-HLA antibodies (DSA)
Adequate hematological, renal, and liver function

Exclusion Criteria:

Active central nervous system (CNS) involvement by malignancy
Current thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy
Any other active malignancies that required systemic treatment within 3 years prior to enrollment
Radiation therapy within 2 weeks prior to ALLO-647
Prior irradiation to >25% of the bone marrow
Hypocellular bone marrow for age by institutional standard as determined from a bone marrow biopsy performed at time of screening
Autologous hematopoietic stem cell transplant (HSCT) within last 6 months (24 weeks)
Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647
Subjects with active systemic bacterial, fungal, or viral infection requiring systemic treatment (including positive blood cultures within 7 days before starting lymphodepletion)

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Allogene Therapeutics Inc.

415-604-5696

clinicaltrials@allogene.com

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04416984

Other Study ID Numbers ^ICMJE

ALLO-501A-201

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

Allogene Therapeutics

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Allogene Therapeutics

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Not Provided

PRS Account

Allogene Therapeutics

Verification Date

February 2023

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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