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NCT Number: NCT04416984

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)

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoma Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Princess Alexandra Hospital, Woolloongabba, Queensland, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ALLO-501A

Genetic

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

ALLO-647

Biological

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

Fludarabine

Drug

Chemotherapy for lymphodepletion

Cyclophosphamide

Drug

Chemotherapy for lymphodepletion

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

Secondary outcomes

  1. 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)

  2. Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator

    Time frame: Up to 60 months

  3. 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

  4. 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

  5. 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

  6. 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

  7. Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count

    Time frame: Up to 9 months

  8. Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery

    Time frame: Up to 9 months

  9. 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

  10. Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax)

    Time frame: Up to 9 months

  11. Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC)

    Time frame: Up to 9 months

  12. Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax)

    Time frame: Up to 9 months

  13. Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC)

    Time frame: Up to 9 months

  14. Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts

    Time frame: Up to 9 months

  15. Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN®

    Time frame: Up to 9 months

  16. Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647

    Time frame: Up to 9 months

  17. 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

  18. 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

  19. 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

Sponsors and collaborators

Lead sponsor

Allogene Therapeutics

Industry

Registry information

Official study title

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)

Acronym: ALPHA2

Important dates

Study start
2020
Primary completion
2029
Study completion
2029
First posted
Jun 4, 2020
Registry last updated
Mar 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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