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)

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: Active, not recruiting
• Conditions: Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma
• Intervention / Treatment: Biological: ALLO-647; Drug: Fludarabine; Drug: Cyclophosphamide; Genetic: ALLO-501A

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital Melbourne
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • QEII Health Sciences Centre-VG Site
  • Quebec
    • Québec, Quebec, Canada, G1J 1Z4
      • CHU de Québec -Université Laval; Hôpital de l'Enfant-Jésus
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Palo Alto, California, United States, 94035
      • Stanford Cancer Institute
  • Colorado
    • Denver, Colorado, United States, 80218-1234
      • Colorado Blood Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 06510
      • Advent Health
    • Tampa, Florida, United States, 33612-9416
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital - Atlanta
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117
      • Avera Medical
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Austin, Texas, United States, 78704
      • St. David's South Austin Medical Center
    • Dallas, Texas, United States, 75251
      • Texas Oncology
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center - University of Texas
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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)	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	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	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		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	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		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	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	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	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)	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		Up to 9 months
Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery		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		Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax)		Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC)		Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax)		Up to 9 months
Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC)		Up to 9 months
Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts		Up to 9 months
Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN®		Up to 9 months
Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647		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	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	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		Up to 60 months

Collaborators and Investigators

• Sponsor: Allogene Therapeutics

Publications and helpful links

General Publications

• Locke FL, Munoz JL, Tees MT, Lekakis LJ, de Vos S, Nath R, Stevens DA, Malik SA, Shouse GP, Hamadani M, Oluwole OO, Perales MA, Miklos DB, Fisher PW, Feng A, Navale L, Le Gall JB, Neelapu SS. Allogeneic Chimeric Antigen Receptor T-Cell Products Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma: Phase I Experience From the ALPHA2/ALPHA Clinical Studies. J Clin Oncol. 2025 May 10;43(14):1695-1705. doi: 10.1200/JCO-24-01933. Epub 2025 Feb 13.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2020
• Primary Completion (Estimated): February 1, 2029
• 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 (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Lymphoma; Leukemia; Allogeneic Cell Therapy; CLL; Chronic Lymphocytic Leukemia; CAR T; SLL; Cellular Immuno-therapy; Small Lymphocytic Lymphoma; AlloCAR T; ALLO-647; LBCL; Large B-Cell Lymphoma; ALLO-501A; Cema-cel; Cemacabtagene ansegedleucel
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• 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