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

Relapsed/Refractory Multiple Myeloma Clinical Trial

— 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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04093596
• Other study ID #: ALLO-715-101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 23, 2019
• Est. completion date: September 2027

Study information

• Verified date: August 2023
• Source: Allogene Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 132
• Est. completion date: September 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Genetic:
• ALLO-715
ALLO-715 is an allogeneic CAR T cell therapy targeting BCMA

Biological:
• ALLO-647
ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen

Drug:
• Fludarabine
Chemotherapy for lymphodepletion
• Cyclophosphamide
Chemotherapy for lymphodepletion
• Nirogacestat
a small molecule, selective, reversible, noncompetitive inhibitor of ?secretase (GSI) that increases BCMA target density on the surface of multiple myeloma cells.

Locations

Country	Name	City	State
United States	St. David's South Austin Medical Center	Austin	Texas
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Sarah Cannon/Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stanford Cancer Institute	Palo Alto	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Texas Transplant Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Allogene Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Erratum In: Nat Med. 2023 Mar 17;: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715	Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.	28 Days
Primary	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.	The proportion of subjects in a dose cohort with DLTs of ALLO-647	33 days
Primary	To assess the overall safety profile and tolerability of nirogacestat given concomitantly with ALLO-715 following lymphodepletion with Flu/ Cy/ ALLO-647.	Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.	28 days
Secondary	Cellular kinetics of ALLO-715	Levels of anti-BCMA CAR T cells in blood	up to 60 months
Secondary	antitumor activity of ALLO-715 in combination with nirogacestat	overall -response rate (ORR)	up to 60 months
Secondary	Cellular kinetics of ALLO-715 in combination with nirogacestat	Levels of anti-BCMA CAR T cells in blood	up to 60 months
Secondary	Pharmacokinetics of ALLO-647	Serum concentration levels of ALLO-647	up to 60 months
Secondary	Pharmacokinetics of nirogacestat	Serum concentration levels of nirogacestat	up to 60 months
Secondary	Incidence of immunogenicity against ALLO-715 and ALLO-647	detection and levels of anti-drug antibodies	up to 60 months
Secondary	Immune monitoring after lymphodepletion regimen	Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells	up to 60 months
Secondary	Anti-tumor activity of ALLO-715	overall response rate	up to 60 months
Secondary	Anti-tumor activity of ALLO-715	duration of response	up to 60 months
Secondary	Anti-tumor activity of ALLO-715	overall survival	up to 60 months
Secondary	Anti-tumor activity of ALLO-715	minimal residual disease	up to 60 months
Secondary	To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat	Overall response rate of ALLO-715 with and without Nirogacestat	up to 60 months