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)

NCT04416984 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ALLO-501A-201
• Study Type: interventional
• Target: 160
• Locations: 3 countries
• Sites: 29

Brief Summary

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.

Conditions

Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma

Keywords

CAR T; Cell Therapy; Allogeneic Cell Therapy; Cellular Immuno-therapy; AlloCAR T; ALLO-501A; ALLO-647; LBCL; Lymphoma; Large B-Cell Lymphoma; Cema-cel; Cemacabtagene ansegedleucel; Leukemia; Chronic Lymphocytic Leukemia; CLL; Small Lymphocytic Lymphoma; SLL

Outcome Measures

Primary Outcomes (4)

• 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

• 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

Secondary Outcomes (19)

• Phase 1a, 1b, and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator

  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

  Up to 60 months

• Phase 1a, 1b, and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator

  Up to 60 months

• Phase 1a, 1b, and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator

  Up to 60 months

Study Arms (1)

ALLO-501A, ALLO-647

EXPERIMENTAL

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

Interventions

ALLO-501A GENETIC

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

ALLO-501A, ALLO-647

ALLO-647 BIOLOGICAL

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

ALLO-501A, ALLO-647

Fludarabine DRUG

Chemotherapy for lymphodepletion

ALLO-501A, ALLO-647

Cyclophosphamide DRUG

Chemotherapy for lymphodepletion

ALLO-501A, ALLO-647

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Allogene Therapeutics: lead

Study Sites (29)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94035, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218-1234, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Advent Health

Orlando, Florida, 06510, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612-9416, United States

Location

Northside Hospital - Atlanta

Atlanta, Georgia, 30342, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Avera Medical

Sioux Falls, South Dakota, 57117, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

St. David's South Austin Medical Center

Austin, Texas, 78704, United States

Location

Texas Oncology

Dallas, Texas, 75251, United States

Location

MD Anderson Cancer Center - University of Texas

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

QEII Health Sciences Centre-VG Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

CHU de Québec -Université Laval; Hôpital de l'Enfant-Jésus

Québec, Quebec, G1J 1Z4, Canada

Location

Related Publications (1)

• 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.

  PMID: 39946666 DERIVED

MeSH Terms

Conditions

Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Leukemia

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 4, 2020
• Study Start: May 21, 2020
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

AU (3); CA (2); US (24)