Clinical Trials /

BCMA-directed CAR-T Cell Therapy in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

NCT04318327

Description:

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 relapsed/refractory multiple myeloma

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: BCMA-directed CAR-T Cell Therapy in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
  • Official Title: Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CADPT07A12101
  • NCT ID: NCT04318327

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
PHE885PHE885

Purpose

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 relapsed/refractory multiple myeloma

Trial Arms

NameTypeDescriptionInterventions
PHE885ExperimentalPatients will receive PHE885
  • PHE885

Eligibility Criteria

        Inclusion Criteria:

          -  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)

          -  Measurable disease as defined by the protocol

          -  ECOG performance status that is either 0 or 1 at screening

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose limiting toxicities (DLT)
Time Frame:24 months
Safety Issue:
Description:Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration

Secondary Outcome Measures

Measure:Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated)
Time Frame:24 Months
Safety Issue:
Description:evaluate the feasibility of the manufacturing process
Measure:ORR (overall response rate): Proportion of subjects with the best overall response (BOR)
Time Frame:month 3, month 6
Safety Issue:
Description:BOR (best overall response) of sCR (stringent complete response) +CR (complete response) +VGPR (very good partial response)+PR (partial response) at Months 3 and 6, as determined by local investigator using the IMWG (International Myeloma Working Group) Criteria (Kumar et al, 2016)
Measure:CRR (complete response rate)
Time Frame:3 months
Safety Issue:
Description:Proportion of subjects with the BOR of sCR+CR at Month 3, as determined by local investigator using the IMWG Criteria.
Measure:DOR (duration of response)
Time Frame:12 months
Safety Issue:
Description:as assessed by local investigator: the time from achievement of sCR+CR+VGPR+PR to relapse or death due to MM (multiple myeloma)
Measure:Cmax of BCMA CAR-T cells
Time Frame:24 months
Safety Issue:
Description:through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
Measure:Tmax of BCMA CAR-T cells
Time Frame:24 months
Safety Issue:
Description:through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
Measure:AUC of BCMA CAR-T cells
Time Frame:24 months
Safety Issue:
Description:through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
Measure:Clast of BCMA CAR-T cells
Time Frame:24 months
Safety Issue:
Description:through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
Measure:number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy
Time Frame:24 Months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Multiple myeloma, B-cell maturation antigen, BCMA, anti-BCMA, BCMA-directed, chimeric antigen receptor, CAR-T, PHE885

Last Updated

July 7, 2020