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

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ClinicalTrials.gov Identifier: NCT03288493
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : March 27, 2020
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Poseida Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE September 13, 2017
First Posted Date  ICMJE September 20, 2017
Last Update Posted Date March 27, 2020
Actual Study Start Date  ICMJE September 20, 2017
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2019)
  • Phase 1: Assess the Safety of P-BCMA-101 [ Time Frame: Baseline through Day 28 ]
    Incidence and severity of treatment-emergent adverse events
  • Phase 1: Maximum tolerated dose of P-BCMA-101 [ Time Frame: Baseline through Day 28 ]
    Rate of dose limiting toxicities (DLT)
  • Phase 2: Assess the safety of P-BCMA-101 [ Time Frame: Baseline through 24 months ]
    Incidence and severity of treatment-emergent adverse events
  • Phase 2: Assess the efficacy of P-BCMA-101 (ORR) [ Time Frame: Baseline through 24 months ]
    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).
  • Phase 2: Assess the efficacy of P-BCMA-101 (DOR) [ Time Frame: Baseline through 24 months ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2017)
Safety and maximum tolerated dose of P-BCMA-101 based on dose limiting toxicities [ Time Frame: Baseline through Day 28 ]
Rate of dose limiting toxicities
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2019)
  • Phase 1:Assess the safety of P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
    Incidence and severity of treatment-emergent adverse events
  • Phase 1:Assess the feasibility P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
    Ability to generate protocol-proscribed doses of P-BCMA-101.
  • Phase 1: Anti-myeloma effect of P-BCMA-101 (ORR) [ Time Frame: Baseline through Month 24 ]
    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).
  • Phase 1: Anti-myeloma effect of P-BCMA-101 (TTR) [ Time Frame: Baseline through Month 24 ]
    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.
  • Phase 1: Anti-myeloma effect of P-BCMA-101 (DOR) [ Time Frame: Baseline through Month 24 ]
    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.
  • Phase 1: Anti-myeloma effect of P-BCMA-101 (PFS) [ Time Frame: Baseline through Month 24 ]
    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.
  • Phase 1: Anti-myeloma effect of P-BCMA-101 (OS) [ Time Frame: Baseline through Month 24 ]
    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.
  • 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 ]
    Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)
  • Phase 2: Incidence and severity of cytokine release syndrome (CRS) [ Time Frame: Baseline through Month 24 ]
    Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)
  • Phase 2: Evaluate Efficacy Endpoints (IL-6) [ Time Frame: Baseline through Month 24 ]
    Rate of IL-6 antagonist
  • Phase 2: Evaluate Efficacy Endpoints (C) [ Time Frame: Baseline through Month 24 ]
    Corticosteroid Use
  • Phase 2: Evaluate Efficacy Endpoints (R) [ Time Frame: Baseline through Month 24 ]
    Rimiducid Use
  • Phase 2: Evaluate Efficacy Endpoints (OS) [ Time Frame: Baseline through Month 24 ]
    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.
  • Phase 2: Evaluate Efficacy Endpoints (PFS) [ Time Frame: Baseline through Month 24 ]
    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.
  • Phase 2: Evaluate Efficacy Endpoints (TTR) [ Time Frame: Baseline through Month 24 ]
    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.
  • Phase 2: Evaluate Efficacy Endpoints (MRD) [ Time Frame: Baseline through Month 24 ]
    Minimum residual disease negative rate
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2017)
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Baseline through Month 24 ]
    Incidence and severity of treatment-emergent adverse events
  • Anti-myeloma effect of P-BCMA-101(Response Rate) [ Time Frame: Baseline through Month 24 ]
    Percentage of patients with complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma.
  • Anti-myeloma effect of P-BCMA-101(Duration of Response) [ Time Frame: Baseline through Month 24 ]
    Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma.
  • Anti-myeloma effect of P-BCMA-101(Progression Free Survival) [ Time Frame: Baseline through Month 24 ]
    Time from P-BCMA-101 treatment to progressive disease according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma.or death
  • Anti-myeloma effect of P-BCMA-101(Overall Survival) [ Time Frame: Baseline through Month 24 ]
    Duration of survival from time of treatment with P-BCMA-101
  • Pharmacokinetics of P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
    Concentration of P-BCMA-101 cells in blood and bone marrow over time
  • Biomarkers for P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
    Levels of BCMA in blood and bone marrow cells
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM)
Official Title  ICMJE Open-Label, Multicenter, Phase 1 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)
Brief Summary Phase 1 of the study is comprised of an open-label, single ascending dose (SAD), multiple cohort study; a multiple dose cycle administration cohort study; and a combination administration 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. 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, with or without combination therapy. Treated patients will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Phase 1: open label, 3 + 3 design of dose-escalating cohorts Phase 2: open label, administered as a total dose
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Biological: P-BCMA-101 CAR-T cells
    P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.
  • Drug: Rimiducid
    Rimiducid (safety switch activator) may be administered as indicated.
Study Arms  ICMJE
  • Experimental: Phase 1: P-BCMA-101 CAR-T cells
    Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells. Rimiducid may be administered as indicated.
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
  • Experimental: Phase 1 P-BCMA-101 CAR-T cells (Cohort A)
    Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
  • Experimental: Phase 1 P-BCMA-101 CAR-T cells (Cohort B)
    Single dose given across three intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
  • Experimental: Phase 1 P-BCMA-101 CAR-T cells (Cohort C)
    Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
  • Experimental: Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R)
    Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
  • Experimental: Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP)
    Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before apheresis. Rimiducid may be administered as indicated.
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
  • Experimental: Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT)
    Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
  • Experimental: Phase 2: P-BCMA-101 CAR-T Cells
    CAR-T cells administered via intravenous infusion as a total dose
    Interventions:
    • Biological: P-BCMA-101 CAR-T cells
    • Drug: Rimiducid
Publications * Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.

*   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
 (submitted: March 25, 2020)
220
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2017)
40
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • Unable to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation. (Cohorts R and RP only).
  • History of thromboembolic disease within the past 6 months, regardless of anticoagulation (Cohorts R and RP only).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Angie Schinkel 858 779 3103 clinicaltrials@poseida.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03288493
Other Study ID Numbers  ICMJE P-BCMA-101-001
Has Data Monitoring Committee Yes
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
Responsible Party Poseida Therapeutics, Inc.
Study Sponsor  ICMJE Poseida Therapeutics, Inc.
Collaborators  ICMJE California Institute for Regenerative Medicine (CIRM)
Investigators  ICMJE
Study Director: Matthew A Spear, M.D. Sponsor Chief Medical Officer
PRS Account Poseida Therapeutics, Inc.
Verification Date March 2020

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