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

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ClinicalTrials.gov Identifier: NCT04093596

Recruitment Status : Recruiting

First Posted : September 18, 2019

Last Update Posted : March 7, 2022

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Allogene Therapeutics

Tracking Information

First Submitted Date ^ICMJE

September 16, 2019

First Posted Date ^ICMJE

September 18, 2019

Last Update Posted Date

March 7, 2022

Actual Study Start Date ^ICMJE

September 23, 2019

Estimated Primary Completion Date

December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 28 days ]
Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.

Original Primary Outcome Measures ^ICMJE

Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715 [ Time Frame: 28 Days ]

Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.

Change History

Current Secondary Outcome Measures ^ICMJE

Cellular kinetics of ALLO-715 [ Time Frame: up to 60 months ]
Levels of anti-BCMA CAR T cells in blood
antitumor activity of ALLO-715 in combination with nirogacestat [ Time Frame: up to 60 months ]
overall -response rate (ORR)
Cellular kinetics of ALLO-715 in combination with nirogacestat [ Time Frame: up to 60 months ]
Levels of anti-BCMA CAR T cells in blood
Pharmacokinetics of ALLO-647 [ Time Frame: up to 60 months ]
Serum concentration levels of ALLO-647
Pharmacokinetics of nirogacestat [ Time Frame: up to 60 months ]
Serum concentration levels of nirogacestat
Incidence of immunogenicity against ALLO-715 and ALLO-647 [ Time Frame: up to 60 months ]
detection and levels of anti-drug antibodies
Immune monitoring after lymphodepletion regimen [ Time Frame: up to 60 months ]
Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells
Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
overall response rate
Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
duration of response
Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
overall survival
Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
minimal residual disease
To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat [ Time Frame: up to 60 months ]
Overall response rate of ALLO-715 with and without Nirogacestat

Original Secondary Outcome Measures ^ICMJE

Proportion of subjects experiencing Dose Limiting Toxicities with ALLO-647 in combination with fludarabine and/or cyclophosphamide, or ALLO-647 alone, prior to ALLO-715 [ Time Frame: 33 days ]
Dose limiting toxicity is defined as ALLO-647-related adverse events with onset within 33 days following first infusion of ALLO-647.
Cellular kinetics of ALLO-715 [ Time Frame: up to 24 months ]
Levels of anti-BCMA CAR T cells in blood
Pharmacokinetics of ALLO-647 [ Time Frame: up to 24 months ]
Serum concentration levels of ALLO-647
Incidence of immunogenicity against ALLO-715 and ALLO-647 [ Time Frame: up to 24 months ]
Immune monitoring after lymphodepletion regimen [ Time Frame: up to 24 months ]
Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells
Anti-tumor activity of ALLO-715 [ Time Frame: up to 24 months ]
overall response rate
Anti-tumor activity of ALLO-715 [ Time Frame: up to 24 months ]
time to response rate
Anti-tumor activity of ALLO-715 [ Time Frame: up to 24 months ]
duration of response
Anti-tumor activity of ALLO-715 [ Time Frame: up to 24 months ]
progression-free survival
Anti-tumor activity of ALLO-715 [ Time Frame: up to 24 months ]
overall survival
Anti-tumor activity of ALLO-715 [ Time Frame: up to 24 months ]
minimal residual disease

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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 Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1

Study Design ^ICMJE

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Relapsed/Refractory Multiple Myeloma

Intervention ^ICMJE

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.

Study Arms ^ICMJE

Experimental: ALLO-647, ALLO-715, Nirogacestat

Interventions:

Genetic: ALLO-715
Biological: ALLO-647
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Nirogacestat

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

132

Original Estimated Enrollment ^ICMJE

Estimated Study Completion Date ^ICMJE

December 2027

Estimated Primary Completion Date

December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Allogene Therapeutics

415-604-5696

clinicaltrials@allogene.com

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04093596

Other Study ID Numbers ^ICMJE

ALLO-715-101

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

Allogene Therapeutics

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Allogene Therapeutics

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Not Provided

PRS Account

Allogene Therapeutics

Verification Date

February 2022

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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