Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT04093596
- Lead Sponsor
- Allogene Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 132
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ALLO-647, ALLO-715, Nirogacestat ALLO-715 - ALLO-647, ALLO-715, Nirogacestat ALLO-647 - ALLO-647, ALLO-715, Nirogacestat Cyclophosphamide - ALLO-647, ALLO-715, Nirogacestat Nirogacestat - ALLO-647, ALLO-715, Nirogacestat Fludarabine -
- Primary Outcome Measures
Name Time Method 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. 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 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. 28 days Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics of nirogacestat up to 60 months Serum concentration levels of nirogacestat
Cellular kinetics of ALLO-715 up to 60 months Levels of anti-BCMA CAR T cells in blood
antitumor activity of ALLO-715 in combination with nirogacestat up to 60 months overall -response rate (ORR)
Cellular kinetics of ALLO-715 in combination with nirogacestat up to 60 months Levels of anti-BCMA CAR T cells in blood
Pharmacokinetics of ALLO-647 up to 60 months Serum concentration levels of ALLO-647
Incidence of immunogenicity against ALLO-715 and ALLO-647 up to 60 months detection and levels of anti-drug antibodies
Immune monitoring after lymphodepletion regimen up to 60 months Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells
To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat up to 60 months Overall response rate of ALLO-715 with and without Nirogacestat
Anti-tumor activity of ALLO-715 up to 60 months minimal residual disease
Trial Locations
- Locations (11)
Stanford Cancer Institute
🇺🇸Palo Alto, California, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
City of Hope
🇺🇸Duarte, California, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Sarah Cannon/Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
St. David's South Austin Medical Center
🇺🇸Austin, Texas, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States