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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04093596
Recruitment Status : Recruiting
First Posted : September 18, 2019
Last Update Posted : March 7, 2022
Sponsor:
Information provided by (Responsible Party):
Allogene Therapeutics

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 23, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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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
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Primary Outcome Measures :
  1. 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.

  2. 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

  3. 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.


Secondary Outcome Measures :
  1. Cellular kinetics of ALLO-715 [ Time Frame: up to 60 months ]
    Levels of anti-BCMA CAR T cells in blood

  2. antitumor activity of ALLO-715 in combination with nirogacestat [ Time Frame: up to 60 months ]
    overall -response rate (ORR)

  3. Cellular kinetics of ALLO-715 in combination with nirogacestat [ Time Frame: up to 60 months ]
    Levels of anti-BCMA CAR T cells in blood

  4. Pharmacokinetics of ALLO-647 [ Time Frame: up to 60 months ]
    Serum concentration levels of ALLO-647

  5. Pharmacokinetics of nirogacestat [ Time Frame: up to 60 months ]
    Serum concentration levels of nirogacestat

  6. Incidence of immunogenicity against ALLO-715 and ALLO-647 [ Time Frame: up to 60 months ]
    detection and levels of anti-drug antibodies

  7. 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

  8. Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
    overall response rate

  9. Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
    duration of response

  10. Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
    overall survival

  11. Anti-tumor activity of ALLO-715 [ Time Frame: up to 60 months ]
    minimal residual disease

  12. 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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04093596


Contacts
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Contact: Allogene Therapeutics 415-604-5696 clinicaltrials@allogene.com

Locations
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United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Sheila Myers    480-256-6168    BMDACCResearch@bannerhealth.com   
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact    833-310-2278      
Stanford Cancer Institute Recruiting
Palo Alto, California, United States, 94305
Contact: Michaela Liedtke, MD    650-498-6000    mliedtke@stanford.edu   
United States, Colorado
Sarah Cannon/Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Katherine Bertolin    720-754-4419    katherine.bertolin@sarahcannon.com   
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02144
Contact: Noopur Raje, MD    617-726-0711    nraje@mgh.harvard.edu   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sham Mailankody, MD    212-639-7053    mailanks@mskcc.org   
Contact: Urvi Shah, MD    12126397053    shahu@mskcc.org   
United States, Ohio
Cleveland Clinic Taussig Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Faiz Anwer, MD    216-445-1469    anwerf@ccf.org   
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37203
Contact: Channing V Dudley, MSN    615-875-8757    channing.v.dudley@vumc.org   
United States, Texas
St. David's South Austin Medical Center Recruiting
Austin, Texas, United States, 78704
Contact: Renee Stojanovic, BSN    512-816-6423    renee.stojanovic@stdavids.com   
Texas Transplant Institute Recruiting
San Antonio, Texas, United States, 78229
Contact    210-575-7800      
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Saurabh Chhabra, MD    414-804-4600    schhabra@mcw.edu   
Sponsors and Collaborators
Allogene Therapeutics
More Information
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Responsible Party: Allogene Therapeutics
ClinicalTrials.gov Identifier: NCT04093596    
Other Study ID Numbers: ALLO-715-101
First Posted: September 18, 2019    Key Record Dates
Last Update Posted: March 7, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
 Cyclophosphamide
Fludarabine
Nirogacestat
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Gamma Secretase Inhibitors and Modulators
Enzyme Inhibitors