Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)

NCT04093596 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ALLO-715-101
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (12)

• Cellular kinetics of ALLO-715

  up to 60 months

• antitumor activity of ALLO-715 in combination with nirogacestat

  up to 60 months

• Cellular kinetics of ALLO-715 in combination with nirogacestat

  up to 60 months

• Pharmacokinetics of ALLO-647

  up to 60 months

• Pharmacokinetics of nirogacestat

  up to 60 months

Study Arms (1)

ALLO-647, ALLO-715, Nirogacestat

EXPERIMENTAL

Genetic: ALLO-715; Biological: ALLO-647; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Nirogacestat

Interventions

ALLO-715 GENETIC

ALLO-715 is an allogeneic CAR T cell therapy targeting BCMA

ALLO-647, ALLO-715, Nirogacestat

ALLO-647 BIOLOGICAL

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

ALLO-647, ALLO-715, Nirogacestat

Fludarabine DRUG

Chemotherapy for lymphodepletion

ALLO-647, ALLO-715, Nirogacestat

Cyclophosphamide DRUG

Chemotherapy for lymphodepletion

ALLO-647, ALLO-715, Nirogacestat

Nirogacestat DRUG

a small molecule, selective, reversible, noncompetitive inhibitor of γsecretase (GSI) that increases BCMA target density on the surface of multiple myeloma cells.

ALLO-647, ALLO-715, Nirogacestat

Eligibility Criteria

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

You may qualify if:

• Documented diagnosis of relapsed/refractory multiple myeloma (MM) with measurable disease (serum, urine, or free light chain \[FLC\]) per International Myeloma Working Group (IMWG) criteria
• At least 3 prior lines of MM therapy, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody (unless contraindicated), and refractory to the last treatment line.
• Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Absence of donor (product)-specific anti-HLA antibodies
• Adequate hematologic, renal, hepatic, pulmonary, and cardiac function

You may not qualify if:

• Current or history of Central Nervous System (CNS) involvement of myeloma or plasma cell leukemia
• Clinically significant CNS disorder
• Current or history of thyroid disorder
• Autologous stem cell transplant within the last 6 weeks, or any allogeneic stem cell transplant
• Prior treatment with anti-BCMA therapy, any gene therapy, any genetically modified cell therapy, or adoptive T cell therapy
• History of HIV infection or acute or chronic active hepatitis B or C infection
• Patients unwilling to participate in an extended safety monitoring period
• Inability to swallow tablets
• Subject has known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat
• Use of strong/moderate CYP3A4 inhibitors, and strong CYP3A4 inducers within 14 days before starting nirogacestat.
• Use of concomitant medications that are known to prolong the QT/QTcF interval

Sponsors & Collaborators

• Allogene Therapeutics: lead

Study Sites (11)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94305, United States

Location

Sarah Cannon/Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37203, United States

Location

St. David's South Austin Medical Center

Austin, Texas, 78704, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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.

  PMID: 36690811 BACKGROUND

• 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.

  PMID: 39584380 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

fludarabine; Cyclophosphamide; nirogacestat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

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: September 16, 2019
• First Posted: September 18, 2019
• Study Start: September 23, 2019
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

US (11)