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The purpose of the UNIVERSAL study is to assess the safety, efficacy, cell kinetics, and immunogenicity of ALLO-715 with or without Nirogacestat in adults with relapsed or refractory multiple myeloma after a lymphodepletion regimen of ALLO-647 in combination with fludarabine and/or cyclophosphamide, or ALLO-647 alone.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALLO-647, ALLO-715, Nirogacestat | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALLO-715 | Genetic | ALLO-715 is an allogeneic CAR T cell therapy targeting BCMA |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715 | Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715. | 28 Days |
| To assess the overall safety profile and tolerability of ALLO-647 in combination with Fludarabine and/or cyclophosphamide or ALLO-647 alone, prior to ALLO-715 to confirm the dose of ALLO-647. | The proportion of subjects in a dose cohort with DLTs of ALLO-647 | 33 days |
| To assess the overall safety profile and tolerability of nirogacestat given concomitantly with ALLO-715 following lymphodepletion with Flu/ Cy/ ALLO-647. | Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715. | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Cellular kinetics of ALLO-715 | Levels of anti-BCMA CAR T cells in blood | up to 60 months |
| antitumor activity of ALLO-715 in combination with nirogacestat | overall -response rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
Additional Exclusion Criteria for Nirogacestat plus ALLO-715 Cohorts
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Banner MD Anderson Cancer Center | Gilbert | Arizona | 85234 | United States | ||
| City of Hope |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36690811 | Background | Mailankody S, Matous JV, Chhabra S, Liedtke M, Sidana S, Oluwole OO, Malik S, Nath R, Anwer F, Cruz JC, Htut M, Karski EE, Lovelace W, Dillon M, Butz E, Ying W, Balakumaran A, Kumar SK. Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. Nat Med. 2023 Feb;29(2):422-429. doi: 10.1038/s41591-022-02182-7. Epub 2023 Jan 23. | |
| 39584380 |
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| ALLO-647 | Biological | ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen |
|
| Fludarabine | Drug | Chemotherapy for lymphodepletion |
|
| Cyclophosphamide | Drug | Chemotherapy for lymphodepletion |
|
| Nirogacestat | Drug | a small molecule, selective, reversible, noncompetitive inhibitor of γsecretase (GSI) that increases BCMA target density on the surface of multiple myeloma cells. |
|
| up to 60 months |
| Cellular kinetics of ALLO-715 in combination with nirogacestat | Levels of anti-BCMA CAR T cells in blood | up to 60 months |
| Pharmacokinetics of ALLO-647 | Serum concentration levels of ALLO-647 | up to 60 months |
| Pharmacokinetics of nirogacestat | Serum concentration levels of nirogacestat | up to 60 months |
| Incidence of immunogenicity against ALLO-715 and ALLO-647 | detection and levels of anti-drug antibodies | up to 60 months |
| Immune monitoring after lymphodepletion regimen | Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells | up to 60 months |
| Anti-tumor activity of ALLO-715 | overall response rate | up to 60 months |
| Anti-tumor activity of ALLO-715 | duration of response | up to 60 months |
| Anti-tumor activity of ALLO-715 | overall survival | up to 60 months |
| Anti-tumor activity of ALLO-715 | minimal residual disease | up to 60 months |
| To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat | Overall response rate of ALLO-715 with and without Nirogacestat | up to 60 months |
| Duarte |
| California |
| 91010 |
| United States |
| Stanford Cancer Institute | Palo Alto | California | 94305 | United States |
| Sarah Cannon/Colorado Blood Cancer Institute | Denver | Colorado | 80218 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio | 44195 | United States |
| Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | 37203 | United States |
| St. David's South Austin Medical Center | Austin | Texas | 78704 | United States |
| Texas Transplant Institute | San Antonio | Texas | 78229 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Derived |
| Abba Moussa D, Vazquez M, Chable-Bessia C, Roux-Portalez V, Tamagnini E, Pedotti M, Simonelli L, Ngo G, Souchard M, Lyonnais S, Chentouf M, Gros N, Marsile-Medun S, Dinter H, Pugniere M, Martineau P, Varani L, Juan M, Calderon H, Naranjo-Gomez M, Pelegrin M. Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches. Emerg Microbes Infect. 2025 Dec;14(1):2432345. doi: 10.1080/22221751.2024.2432345. Epub 2024 Dec 9. |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| D003520 | Cyclophosphamide |
| C550722 | nirogacestat |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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