Description:
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.
Title
- Brief Title: Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
ALLO-715-101
- NCT ID:
NCT04093596
Conditions
- Relapsed/Refractory Multiple Myeloma
Interventions
Drug | Synonyms | Arms |
---|
ALLO-647 | | ALLO-647, ALLO-715, Nirogacestat |
Fludarabine | | ALLO-647, ALLO-715, Nirogacestat |
Cyclophosphamide | | ALLO-647, ALLO-715, Nirogacestat |
Nirogacestat | | ALLO-647, ALLO-715, Nirogacestat |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
ALLO-647, ALLO-715, Nirogacestat | Experimental | | - ALLO-647
- Fludarabine
- Cyclophosphamide
- Nirogacestat
|
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715 |
Time Frame: | 28 Days |
Safety Issue: | |
Description: | Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715. |
Secondary Outcome Measures
Measure: | Cellular kinetics of ALLO-715 |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | Levels of anti-BCMA CAR T cells in blood |
Measure: | antitumor activity of ALLO-715 in combination with nirogacestat |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | overall -response rate (ORR) |
Measure: | Cellular kinetics of ALLO-715 in combination with nirogacestat |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | Levels of anti-BCMA CAR T cells in blood |
Measure: | Pharmacokinetics of ALLO-647 |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | Serum concentration levels of ALLO-647 |
Measure: | Pharmacokinetics of nirogacestat |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | Serum concentration levels of nirogacestat |
Measure: | Incidence of immunogenicity against ALLO-715 and ALLO-647 |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | detection and levels of anti-drug antibodies |
Measure: | Immune monitoring after lymphodepletion regimen |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells |
Measure: | Anti-tumor activity of ALLO-715 |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | overall response rate |
Measure: | Anti-tumor activity of ALLO-715 |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | duration of response |
Measure: | Anti-tumor activity of ALLO-715 |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | overall survival |
Measure: | Anti-tumor activity of ALLO-715 |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | minimal residual disease |
Measure: | To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat |
Time Frame: | up to 36 months |
Safety Issue: | |
Description: | Overall response rate of ALLO-715 with and without Nirogacestat |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Allogene Therapeutics |
Last Updated
June 24, 2021