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

April 19, 2024 updated by: Allogene Therapeutics

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)

This is a single-arm, open label, multicenter Phase 1/2 study evaluating ALLO-501A in adult subjects with R/R LBCL and CLL/SLL. The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma and assess the safety of ALLO-501A in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Active, not recruiting
        • Princess Alexandra Hospital
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Active, not recruiting
        • Monash Medical Centre
      • Fitzroy, Victoria, Australia, 3065
        • Active, not recruiting
        • St. Vincent's Hospital Melbourne
      • Melbourne, Victoria, Australia, 3004
        • Withdrawn
        • The Alfred Hospital
  • Canada
      • Québec, Canada, G1J 1Z4
        • Active, not recruiting
        • CHU de Québec -Université Laval; Hôpital de l'Enfant-Jésus
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Withdrawn
        • Vancouver General Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Active, not recruiting
        • QEII Health Sciences Centre-VG Site
  • Italy
      • Bologna, Italy, 40138
        • Withdrawn
        • Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
      • Milan, Italy, 20132
        • Withdrawn
        • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele
      • Torino, Italy, 10126
        • Withdrawn
        • Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
  • Spain
      • Barcelona, Spain, 08035
        • Withdrawn
        • Hospital Universitari Vall d'Hebron
      • Donostia-San Sebastian, Spain, 20014
        • Withdrawn
        • Hospital Universitario Donostia
      • Madrid, Spain, 28046
        • Withdrawn
        • Hospital Universitario La Paz
      • Madrid, Spain, 28041
        • Withdrawn
        • Hospital Universitario 12 de Octubre
      • Salamanca, Spain, 37007
        • Withdrawn
        • Complot Asistencial Universitario de Salamanca - Hospital Clínico
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital
        • Contact:
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
      • Los Angeles, California, United States, 90095
      • Palo Alto, California, United States, 94035
        • Recruiting
        • Stanford Cancer Institute
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218-1234
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Withdrawn
        • Yale School of Medicine
    • Florida
      • Miami, Florida, United States, 33136
        • Active, not recruiting
        • University of Miami
      • Orlando, Florida, United States, 06510
      • Tampa, Florida, United States, 33612-9416
    • Georgia
      • Atlanta, Georgia, United States, 30342
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Augusta University
        • Contact:
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Recruiting
        • Loyola University Medical Center
        • Contact:
    • Kentucky
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Withdrawn
        • Memorial Sloan Kettering Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Withdrawn
        • Providence Portland Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Active, not recruiting
        • Allegheny General Hospital
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117
        • Withdrawn
        • Avera Medical
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt Ingram Cancer Center
        • Contact:
    • Texas
      • Austin, Texas, United States, 78704
      • Dallas, Texas, United States, 75251
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center - University of Texas
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Completed
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

For subjects with LBCL:

  • 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
  • Absence of significant donor (product)-specific anti-HLA antibodies (DSA) at screening (Note: Only applicable for Phase 2)

For subjects with CLL/SLL:

  • Diagnosis of CLL/SLL
  • Relapsed/refractory disease
  • Subjects relapsed/refractory to BTKi therapy and high-risk disease
  • Subjects relapsed/refractory with 2 or more lines of therapy including BTKi and BCL-2 inhibitor (venetoclax)
  • At least 1 measurable lesion at time of enrollment

For all subjects:

  • Male or female subjects ≥18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • 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 (Note: Only applicable for Phase 2).
  • Autologous hematopoietic stem cell transplant (HSCT) within last 6 months (24 weeks)
  • Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ALLO-501A, ALLO-647
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 60 months
Phase 1a: 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
28 days
Phase 1a: Proportion of subjects 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
33 days
Phase 1b: Frequency and severity of ALLO-501A treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest
Time Frame: Up to 60 months
Up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1a, 1b, 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)
Up to 60 months
Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator
Time Frame: Up to 60 months
Up to 60 months
Phase 1a, 1b, 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
Up to 60 months
Phase 1a, 1b, 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
Up to 60 months
Phase 1a, 1b, 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
Up to 60 months
Phase 1a, 1b, and 2: Overall Survival (OS)
Time Frame: Up to 60 months
OS, defined as the time from the enrollment date to death
Up to 60 months
Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, 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
Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax)
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC)
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax)
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC)
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN®
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647
Time Frame: Up to 9 months
Up to 9 months
Phase 1a, 1b, 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
Up to 60 months
Phase 1a, 1b, 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
Up to 60 months
Phase 1a, 1b, and 2: The incidence and severity of clinically significant laboratory toxicities and relationship to ALLO-647
Time Frame: Up to 60 months
Up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Allogene Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 21, 2020

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

May 29, 2020

First Submitted That Met QC Criteria

June 2, 2020

First Posted (Actual)

June 4, 2020

Study Record Updates

Last Update Posted (Estimated)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALLO-501A-201

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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