Clinical trial NCT04093596: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: Allogene Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-09-18
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715
timeFrame: 28 Days
measure: 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.
timeFrame: 33 days
measure: To assess the overall safety profile and tolerability of nirogacestat given concomitantly with ALLO-715 following lymphodepletion with Flu/ Cy/ ALLO-647.
timeFrame: 28 days
Secondary outcomes:
measure: Cellular kinetics of ALLO-715
timeFrame: up to 60 months
measure: antitumor activity of ALLO-715 in combination with nirogacestat
timeFrame: up to 60 months
measure: Cellular kinetics of ALLO-715 in combination with nirogacestat
timeFrame: up to 60 months
measure: Pharmacokinetics of ALLO-647
timeFrame: up to 60 months
measure: Pharmacokinetics of nirogacestat
timeFrame: up to 60 months
measure: Incidence of immunogenicity against ALLO-715 and ALLO-647
timeFrame: up to 60 months
measure: Immune monitoring after lymphodepletion regimen
timeFrame: up to 60 months
measure: Anti-tumor activity of ALLO-715
timeFrame: up to 60 months
measure: Anti-tumor activity of ALLO-715
timeFrame: up to 60 months
measure: Anti-tumor activity of ALLO-715
timeFrame: up to 60 months
measure: Anti-tumor activity of ALLO-715
timeFrame: up to 60 months
measure: To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat
timeFrame: up to 60 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Denver
country: United States
facility: Sarah Cannon/Colorado Blood Cancer Institute
state: Colorado
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin Medical Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References:
citation: 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.