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

Sponsor

Allogene Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04093596

Collaborator

(none)

132

Enrollment

Locations

Arm

98.3

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Multiple Myeloma	Genetic: ALLO-715 Biological: ALLO-647 Drug: Fludarabine Drug: Cyclophosphamide Drug: Nirogacestat	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 23, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALLO-647, ALLO-715, Nirogacestat	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 Drug: Cyclophosphamide Chemotherapy for lymphodepletion Drug: Nirogacestat a small molecule, selective, reversible, noncompetitive inhibitor of γsecretase (GSI) that increases BCMA target density on the surface of multiple myeloma cells.

Arm

Intervention/Treatment

Experimental: ALLO-647, ALLO-715, Nirogacestat

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

Drug: Cyclophosphamide

Chemotherapy for lymphodepletion

Drug: Nirogacestat

a small molecule, selective, reversible, noncompetitive inhibitor of γsecretase (GSI) that increases BCMA target density on the surface of multiple myeloma cells.

Outcome Measures

Primary Outcome Measures

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 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
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

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
Pharmacokinetics of nirogacestat [up to 60 months]
Serum concentration levels of nirogacestat
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
Anti-tumor activity of ALLO-715 [up to 60 months]
overall response rate
Anti-tumor activity of ALLO-715 [up to 60 months]
duration of response
Anti-tumor activity of ALLO-715 [up to 60 months]
overall survival
Anti-tumor activity of ALLO-715 [up to 60 months]
minimal residual disease
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	City of Hope	Duarte	California	United States	91010
3	Stanford Cancer Institute	Palo Alto	California	United States	94305
4	Sarah Cannon/Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
5	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02144
6	Mayo Clinic	Rochester	Minnesota	United States	55905
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
8	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
9	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37203
10	St. David's South Austin Medical Center	Austin	Texas	United States	78704
11	Texas Transplant Institute	San Antonio	Texas	United States	78229
12	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

Allogene Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Allogene Therapeutics

ClinicalTrials.gov Identifier:

NCT04093596

Other Study ID Numbers:

ALLO-715-101

First Posted:

Sep 18, 2019

Last Update Posted:

Mar 7, 2022

Last Verified:

Feb 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Multiple Myeloma

Neoplasms, Plasma Cell

Cyclophosphamide

Fludarabine

Study Results

No Results Posted as of Mar 7, 2022