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

Allogene Therapeutics

Status and phase: Active, not recruiting; Phase 1

Conditions: Relapsed/Refractory Multiple Myeloma

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04093596

ALLO-715-101

Details and patient eligibility

About

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.

Enrollment: 132 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Additional Exclusion Criteria for Nirogacestat plus ALLO-715 Cohorts

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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132 participants in 1 patient group

ALLO-647, ALLO-715, Nirogacestat

Experimental group

Treatment:

Biological: ALLO-647

Drug: Fludarabine

Genetic: ALLO-715

Drug: Nirogacestat

Drug: Cyclophosphamide