The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04416984
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : June 6, 2024
Sponsor:
Information provided by (Responsible Party):
Allogene Therapeutics

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.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma Genetic: ALLO-501A Biological: ALLO-647 Drug: Fludarabine Drug: Cyclophosphamide Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : May 21, 2020
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : May 2029


Arm Intervention/treatment
Experimental: ALLO-501A, ALLO-647 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




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04416984


Contacts
Layout table for location contacts
Contact: Allogene Therapeutics Inc. 415-604-5696 clinicaltrials@allogene.com

Locations
Show Show 39 study locations
Sponsors and Collaborators
Allogene Therapeutics
Layout table for additonal information
Responsible Party: Allogene Therapeutics
ClinicalTrials.gov Identifier: NCT04416984    
Other Study ID Numbers: ALLO-501A-201
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: June 6, 2024
Last Verified: June 2024

Layout table for additional information
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
Keywords provided by Allogene Therapeutics:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists