Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma (ALPHA2) (ALPHA2)
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| ClinicalTrials.gov Identifier: NCT04416984 |
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Recruitment Status :
Recruiting
First Posted : June 4, 2020
Last Update Posted : February 9, 2023
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Sponsor:
Allogene Therapeutics
Information provided by (Responsible Party):
Allogene Therapeutics
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Brief Summary:
The purpose of the ALPHA-2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed/Refractory Large B Cell Lymphoma | Genetic: ALLO-501A Biological: ALLO-647 Drug: Fludarabine Drug: Cyclophosphamide | Phase 1 Phase 2 |
| 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 :
- Phase 1: 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
- Phase 1: Proportion of patients 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
- 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 :
- Phase 1 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)
- Phase 1 and 2: Overall Response Rate (ORR) assessed per investigator [ Time Frame: Up to 60 months ]
- Phase 1 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
- Phase 1 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
- Phase 1 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
- Phase 1 and 2: Overall Survival (OS) [ Time Frame: Up to 60 months ]OS, defined as the time from the enrollment date to death
- Phase 1 and 2: Depth of lymphodepletion as assessed by lymphocyte count [ Time Frame: Up to 9 months ]
- Phase 1 and 2: Duration of lymphodepletion as assessed by lymphocyte recovery [ Time Frame: Up to 9 months ]
- Phase 1 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 ]
- Phase 1 and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax) [ Time Frame: Up to 9 months ]
- Phase 1 and 2: ALLO-501A expansion assessed by area under the curve (AUC) [ Time Frame: Up to 9 months ]
- Phase 1 and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax) [ Time Frame: Up to 9 months ]
- Phase 1 and 2: ALLO-501A persistence assessed by area under the curve (AUC) [ Time Frame: Up to 9 months ]
- Phase 1 and 2: Pharmacodynamics will be evaluated on host T cell counts [ Time Frame: Up to 9 months ]
- Phase 1 and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN® [ Time Frame: Up to 9 months ]
- Phase 1 and 2: The incidence of anti-drug antibodies against ALLO-647 [ Time Frame: Up to 9 months ]
- Phase 1 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
- Phase 1 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
- Phase 1 and 2: The incidence and severity of clinically significant laboratory toxicities [ Time Frame: Up to 60 months ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
- ECOG performance status 0 or 1
- Absence of donor (product)-specific anti-HLA antibodies (DSA)
- 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
- Autologous hematopoietic stem cell transplant (HSCT) within last 6 months (24 weeks)
- Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647
- Subjects with active systemic bacterial, fungal, or viral infection requiring systemic treatment (including positive blood cultures within 7 days before starting lymphodepletion)
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
| Contact: Allogene Therapeutics Inc. | 415-604-5696 | clinicaltrials@allogene.com |
Locations
Show 17 study locations
Sponsors and Collaborators
Allogene Therapeutics
| 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: | February 9, 2023 |
| Last Verified: | February 2023 |
| 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:
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CAR T Cell Therapy Allogeneic Cell Therapy Cellular Immuno-therapy AlloCAR T |
ALLO-501A ALLO-647 LBCL Lymphoma Large B-Cell Lymphoma |
Additional relevant MeSH terms:
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Lymphoma Lymphoma, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin 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 |