A Single-Arm, Open-Label, Phase 1 Study of the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-715 to Evaluate an Anti-BCMA Allogeneic CAR T Cell Therapy With or Without Nirogacestat in Subjects With Relapsed/Refractory Multiple Myeloma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Allogene Therapeutics
- Enrollment
- 73
- Locations
- 21
- Primary Endpoint
- 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.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
ALLO-647, ALLO-715, Nirogacestat
Intervention: Fludarabine (Drug)
ALLO-647, ALLO-715, Nirogacestat
Intervention: Cyclophosphamide (Drug)
ALLO-647, ALLO-715, Nirogacestat
Intervention: Nirogacestat (Drug)
ALLO-647, ALLO-715, Nirogacestat
Intervention: ALLO-715 (Genetic)
ALLO-647, ALLO-715, Nirogacestat
Intervention: ALLO-647 (Biological)
Outcomes
Primary Outcomes
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.
Time Frame: 33 days
The proportion of subjects in a dose cohort with DLTs of ALLO-647
Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715
Time Frame: 28 Days
Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.
To assess the overall safety profile and tolerability of nirogacestat given concomitantly with ALLO-715 following lymphodepletion with Flu/ Cy/ ALLO-647.
Time Frame: 28 days
Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.
Secondary Outcomes
- Pharmacokinetics of nirogacestat(up to 60 months)
- 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)
- Incidence of immunogenicity against ALLO-715 and ALLO-647(up to 60 months)
- Immune monitoring after lymphodepletion regimen(up to 60 months)
- To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat(up to 60 months)
- Anti-tumor activity of ALLO-715(up to 60 months)