Clinical Trials /

P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM)

NCT03288493

Description:

A Phase 1, open-label, single ascending dose (SAD) study of P-BCMA-101 autologous T stem cell memory (Tscm) CAR-T cells in patients with relapsed / refractory MM. Followed by a Phase 2 open-label efficacy and safety study. Rimiducid may be administered as indicated.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM)
  • Official Title: Open-Label, Multicenter, Single Ascending Dose Study to Assess the Safety of P-BCMA-101 in Subjects With Relapsed / Refractory Multiple Myeloma (MM) Followed by a Phase 2 Assessment of Response and Safety (PRIME)

Clinical Trial IDs

  • ORG STUDY ID: P-BCMA-101-001
  • NCT ID: NCT03288493

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
P-BCMA-101 CAR-T cellsPhase 1: P-BCMA-101 CAR-T cells
RimiducidPhase 1: P-BCMA-101 CAR-T cells

Purpose

A Phase 1, open-label, single ascending dose (SAD) study of P-BCMA-101 autologous T stem cell memory (Tscm) CAR-T cells in patients with relapsed / refractory MM. Followed by a Phase 2 open-label efficacy and safety study. Rimiducid may be administered as indicated.

Detailed Description

      Phase 1 follows a 3 + 3 design of dose-escalating cohorts. Phase 2 of the study is an
      open-label multi-center efficacy and safety study containing a two arm cycle dosing regime.
      After a patient enrolls, leukapheresis will be performed to obtain peripheral blood
      mononuclear cells which will be sent to a manufacturing site to produce P-BCMA-101 CAR-T
      cells. The cells will then be returned to the investigational site and, after a standard
      chemotherapy based conditioning regimen, will be administered to the patient across 1-3
      infusions. Treated patients will undergo serial measurements of safety, tolerability and
      response. Rimiducid may be administered as indicated.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: P-BCMA-101 CAR-T cellsExperimentalSingle ascending dose cohorts, given in a single intravenous infusion of CAR-T cells. Rimiducid may be administered as indicated.
  • P-BCMA-101 CAR-T cells
  • Rimiducid
Phase 2 P-BCMA-101 CAR-T cells (Cohort A)ExperimentalSingle dose given across two intravenous infusion pf CAR-T cells. Rimiducid may be administered as indicated.
  • P-BCMA-101 CAR-T cells
  • Rimiducid
Phase 2 P-BCMA-101 CAR-T cells (Cohort B)ExperimentalSingle dose given across three intravenous infusion of CAR-T cells. Rimiducid may be administered as indicated.
  • P-BCMA-101 CAR-T cells
  • Rimiducid

Eligibility Criteria

        Inclusion Criteria:

          -  Males or females, ≥18 years of age

          -  Must have a confirmed diagnosis of active MM

          -  Must have measurable MM

          -  Must have relapsed / refractory MM, having received treatment with proteasome
             inhibitor and IMiD [Phase 2: Must have relapsed / refractory MM, and refractory to
             last line of therapy, having received treatment with proteasome inhibitor, an IMiD,
             CD38 targeted therapy and undergone autologous stem cell transplant (ASCT) or not a
             candidate for ASCT.]

          -  Must have adequate hepatic, renal, cardiac and hematopoietic function

        Exclusion Criteria:

          -  Is pregnant or lactating

          -  Has inadequate venous access and/or contraindications to leukapheresis

          -  Has active hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia,
             POEMS syndrome, disseminated intravascular coagulation, leukostasis, amyloidosis,
             significant autoimmune, CNS or other malignant disease

          -  Has an active second malignancy (not disease-free for at least 5 years) in addition to
             MM, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell
             skin carcinoma.

          -  Has active autoimmune disease

          -  Has a history of significant central nervous system (CNS) disease, such as stroke,
             epilepsy, etc.

          -  Has an active systemic infection

          -  Has hepatitis B or C virus, human immunodeficiency virus (HIV), or human
             T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome.

          -  Has any psychiatric or medical disorder that would preclude safe participation in
             and/or adherence to the protocol

          -  Has receiving immunosuppressive or other contraindicated therapies within the excluded
             time frame from entry

          -  Has CNS metastases or symptomatic CNS involvement

          -  Has a history of having undergone allogeneic stem cell transplantation, or any other
             allogeneic or xenogeneic transplant, or has undergone autologous transplantation
             within 90 days.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Assess the Safety of P-BCMA-101
Time Frame:Baseline through Day 28
Safety Issue:
Description:Incidence and severity of treatment-emergent adverse events

Secondary Outcome Measures

Measure:Phase 1:Assess the safety of P-BCMA-101
Time Frame:Baseline through Month 24
Safety Issue:
Description:Incidence and severity of treatment-emergent adverse events
Measure:Phase 1:Assess the feasibility P-BCMA-101
Time Frame:Baseline through Month 24
Safety Issue:
Description:Ability to generate protocol-proscribed doses of P-BCMA-101.
Measure:Phase 1: Anti-myeloma effect of P-BCMA-101 (ORR)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Overall Response Rate (ORR)-Percentage of patients with complete response (CR), very good partial response (VGPR), or partial response (PR).
Measure:Phase 1: Anti-myeloma effect of P-BCMA-101 (TTR)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Time to Response (TTR)-Time to complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.
Measure:Phase 1: Anti-myeloma effect of P-BCMA-101 (DOR)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Duration of Response (DOR)-Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.
Measure:Phase 1: Anti-myeloma effect of P-BCMA-101 (PFS)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Progression Free Survival (PFS)-Time from P-BCMA-101 treatment to progressive disease.
Measure:Phase 1: Anti-myeloma effect of P-BCMA-101 (OS)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Overall Survival (OS)-Duration of survival from time of treatment with P-BCMA-101.
Measure:Phase 1: The effect of cell dose to guide selection of doses for further assessment in Phase 2/3 studies
Time Frame:Baseline through Month 24
Safety Issue:
Description:Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)
Measure:Phase 2: Incidence and severity of cytokine release syndrome (CRS)
Time Frame:Baseline through Month 24
Safety Issue:
Description:Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)
Measure:Phase 2: Evaluate Efficacy Endpoints (IL-6)
Time Frame:Baseline through Month 24
Safety Issue:
Description:Rate of IL-6 antagonist
Measure:Phase 2: Evaluate Efficacy Endpoints (C)
Time Frame:Baseline through Month 24
Safety Issue:
Description:Corticosteroid Use
Measure:Phase 2: Evaluate Efficacy Endpoints (R)
Time Frame:Baseline through Month 24
Safety Issue:
Description:Rimiducid Use
Measure:Phase 2: Evaluate Efficacy Endpoints (OS)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Overall Survival (OS)-Duration of survival from time of treatment with P-BCMA-101.
Measure:Phase 2: Evaluate Efficacy Endpoints (PFS)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Progression Free Survival (PFS)-Time from P-BCMA-101 treatment to progressive disease.
Measure:Phase 2: Evaluate Efficacy Endpoints (TTR)
Time Frame:Baseline through Month 24
Safety Issue:
Description:According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Time to Response (TTR)-Time to complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.
Measure:Phase 2: Evaluate Efficacy Endpoints (MRD)
Time Frame:Baseline through Month 24
Safety Issue:
Description:Minimum residual disease negative rate

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Poseida Therapeutics, Inc.

Trial Keywords

  • CAR-T cells

Last Updated

November 14, 2019