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BCMA-directed CAR-T Cell Therapy in Adult Patients With Multiple Myeloma

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04318327
Recruitment Status : Active, not recruiting
First Posted : March 23, 2020
Last Update Posted : January 25, 2024
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous T cells genetically engineered with a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) and manufactured with a new process. CAR-T cells will be investigated as a single agent in multiple myeloma

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: PHE885 Phase 1

Detailed Description:
This is a phase I, open label study to characterize the safety and tolerability of a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) manufactured with a new process. In the dose escalation part (Part A) of the study, the anti-BCMA CAR-T cell therapy will be studied in adult multiple myeloma (MM) subjects who are relapsed and/or refractory. In the dose evaluation part (Part B) of the study, the anti-BCMA CAR-T cell therapy will be studied in newly diagnosed adult subject with MM.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Multiple Myeloma
Actual Study Start Date : July 23, 2020
Estimated Primary Completion Date : February 19, 2026
Estimated Study Completion Date : February 19, 2026

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: PHE885 (Part A)
Relapsed and/or refractory multiple myeloma (r/r MM) patients will receive PHE885.
 Biological: PHE885
Infusion
Experimental: PHE885 (Part B)
Newly diagnosed multiple myeloma (NDMM) patients will receive PHE885.
 Biological: PHE885
Infusion


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Dose limiting toxicities (DLT) [ Time Frame: 28 days ]
    Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration

  2. Nature of Dose limiting toxicities (DLT) [ Time Frame: 28 days ]
    Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration

  3. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated) [ Time Frame: 24 Months ]
    evaluate the feasibility of the manufacturing process

  2. Overall Response Rate (ORR) in Part A [ Time Frame: 24 months ]
    Proportion of subjects with the best overall response (BOR) of PR (partial response) or better, as determined by local investigator using the IMWG Criteria

  3. ORR in Part B [ Time Frame: 24 months ]
    Proportion of subjects with VGPR (very good partial response) or PR to induction therapy who achieve the BOR of PR or better, as determined by local investigator using the IMWG Criteria

  4. Response rate at 3 and 6 months in Part A [ Time Frame: 3 months, 6 months ]
    Proportion of subjects with the overall response of PR or better at months 3 and 6 after infusion respectively, as determined by local investigator using the IMWG Criteria

  5. Overall response rate at 3 and 6 months in Part B [ Time Frame: 3 months, 6 months ]
    Proportion of subjects with VGPR or PR to induction therapy who achieve the overall response of PR or better at months 3 and 6 after infusion respectively, as determined by local investigator using the IMWG Criteria

  6. Overall Complete Response Rate (CRR) in Part A [ Time Frame: 24 months ]
    Proportion of subjects with the BOR of CR or better, as determined by local investigator using the IMWG Criteria

  7. Overall CRR in Part B [ Time Frame: 24 months ]
    Proportion of subjects with a response of VGPR or PR to induction therapy with the BOR of CR or better, as determined by local investigator using the IMWG Criteria

  8. CRR at months 3 and 6 in Part A [ Time Frame: 3 months, 6 months ]
    Proportion of subjects with the overall response of CR or better at months 3 and 6 respectively, as determined by local investigator using the IMWG Criteria

  9. CRR at months 3 and 6 in Part B [ Time Frame: 3 months, 6 months ]
    Proportion of subjects with a response of VGPR or PR to induction therapy with the overall response of CR or better at months 3 and 6 after infusion, respectively, as determined by local investigator using the IMWG Criteria

  10. DOR (duration of response) in Part A [ Time Frame: from disease response to disease progression, assessed up to approximately 24 months ]
    DOR as assessed by local investigator: the time from achievement of PR or better to relapse or death due to MM (multiple myeloma)

  11. DOR in Part B [ Time Frame: from disease response to disease progression, assessed up to approximately 24 months ]

    DOR as assessed by local investigator:

    • The time from the first documented disease response after infusion of CR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy, and
    • The time from the first documented disease response after infusion of PR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy

  12. Cmax of BCMA CAR-T cells [ Time Frame: 24 months ]
    through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow

  13. Tmax of BCMA CAR-T cells [ Time Frame: 24 months ]
    through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow

  14. AUC of BCMA CAR-T cells [ Time Frame: 24 months ]
    through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow

  15. Clast of BCMA CAR-T cells [ Time Frame: 24 months ]
    through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow

  16. number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy [ Time Frame: 24 Months ]

Eligibility Criteria
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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:

  • Part A: Subjects with MM who are relapsed and/or refractory to at least 2 prior treatment regimens, including an IMiD (e.g. lenalidomide or pomalidomide), a proteasome inhibitor (e.g. bortezomib, carfilzomib), and an approved anti-CD38 antibody (e.g. daratumumab), if available, and have documented evidence of disease progression (IMWG criteria)
  • Part A: ECOG performance status that is either 0 or 1 at screening
  • Part B: Subjects with newly diagnosed multiple myeloma (NDMM) who have received a minimum of 4 and up to 6 cycles of standard induction therapy with VRd, D-VRd, or D-Rd, and have achieved a response of PR or better. One cycle of CyBorDex is allowed prior to induction.
  • Part B: ECOG performance status that is either 0,1 or 2 at screening
  • Measurable disease as defined by the protocol
  • Adequate hematological values
  • Must have a leukapheresis material of non-mobilized cells accepted for manufacturing

Exclusion Criteria:

  • Prior administration of a genetically modified cellular product including prior BCMA CAR-T therapy. Patients who have received prior BCMA-directed bi-specific antibodies or antibody-drug conjugates (ADC) are not excluded.
  • Autologous HSCT within 6 weeks prior to enrollment or any prior history of allogeneic hematopoietic stem cell transplant (HSCT)
  • Chemotherapy or any concomitant anti-cancer therapies (other than protocol prescribed lymphodepletion (LD) chemotherapy) within 2 weeks prior to apheresis
  • Treatment with small molecule targeted antineoplastics within 2 weeks of apheresis collection or 5 half-lives whichever is shorter
  • Have received antibodies or immunotherapies (other than daratumumab) within 4 weeks prior to apheresis collection. Daratumumab within 3 weeks prior to apheresis collection.
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): NCT04318327


Locations
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United States, Illinois
University of Chicago Medical Center Hematology and Oncology
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas Cancer Center .
Westwood, Kansas, United States, 66205
United States, Massachusetts
Beth Israel Deaconess Medical Cente KS121
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute Main Centre
Boston, Massachusetts, United States, 02215
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, Victoria
Novartis Investigative Site
Prahran, Victoria, Australia, 3181
Australia
Novartis Investigative Site
Camperdown, Australia, NSW
Israel
Novartis Investigative Site
Haifa, Israel, 3109601
Novartis Investigative Site
Ramat Gan, Israel, 52621
Novartis Investigative Site
Tel Aviv, Israel, 6423906
Singapore
Novartis Investigative Site
Singapore, Singapore, 119228
Novartis Investigative Site
Singapore, Singapore, 169608
Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04318327    
Other Study ID Numbers: CADPT07A12101
First Posted: March 23, 2020    Key Record Dates
Last Update Posted: January 25, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Multiple myeloma
B-cell maturation antigen
BCMA
anti-BCMA
 BCMA-directed
chimeric antigen receptor
CAR-T
PHE885
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