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

March 26, 2024 updated by: Poseida Therapeutics, Inc.

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

105

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
    • California
      • Davis, California, United States, 95618
        • University of California Davis
      • San Diego, California, United States, 92093
        • University of California San Diego
      • San Francisco, California, United States, 94143
        • University of California San Francisco
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Kansas
      • Westwood, Kansas, United States, 66205
        • University of Kansas Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Johns Hopkins University
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Greenebaum Comprehensive Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State - Karmanos Cancer Institute
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute at Tennessee Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Experimental: Phase 2: P-BCMA-101 CAR-T Cells
CAR-T cells administered via intravenous infusion as a total dose
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Assess the Safety of P-BCMA-101
Time Frame: Baseline through Day 28
Incidence and severity of treatment-emergent adverse events
Baseline through Day 28
Phase 1: Maximum Tolerated Dose of P-BCMA-101
Time Frame: Baseline through Day 28
Rate of dose limiting toxicities (DLT)
Baseline through Day 28
Phase 2: Assess the Safety of P-BCMA-101
Time Frame: Baseline through 24 months
Incidence and severity of treatment-emergent adverse events
Baseline through 24 months
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).
Baseline through 24 months
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.
Baseline through 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2: Evaluate Efficacy Endpoints (IL-6)
Time Frame: Baseline through Month 24
Rate of IL-6 antagonist
Baseline through Month 24
Phase 2: Evaluate Efficacy Endpoints (C)
Time Frame: Baseline through Month 24
Corticosteroid Use
Baseline through Month 24
Phase 2: Evaluate Efficacy Endpoints (R)
Time Frame: Baseline through Month 24
Rimiducid Use
Baseline through Month 24
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.
Baseline through Month 24
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.
Baseline through Month 24
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.
Baseline through Month 24
Phase 2: Evaluate Efficacy Endpoints (MRD)
Time Frame: Baseline through Month 24
Minimum residual disease negative rate
Baseline through Month 24
Phase 1:Assess the Safety of P-BCMA-101
Time Frame: Baseline through Month 24
Incidence and severity of treatment-emergent adverse events
Baseline through Month 24
Phase 1:Assess the Feasibility P-BCMA-101
Time Frame: Baseline through Month 24
Ability to generate protocol-prescribed doses of P-BCMA-101.
Baseline through Month 24
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).
Baseline through Month 24
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.
Baseline through Month 24
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.
Baseline through Month 24
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.
Baseline through Month 24
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.
Baseline through Month 24
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)
Baseline through Month 24
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)
Baseline through Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Poseida Therapeutics, Inc.

Collaborators

California Institute for Regenerative Medicine (CIRM)

Investigators

  • Study Director: Rajesh Belani, M.D., Sponsor Executive Medical Director

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2017

Primary Completion (Actual)

April 27, 2022

Study Completion (Actual)

April 27, 2022

Study Registration Dates

First Submitted

September 13, 2017

First Submitted That Met QC Criteria

September 18, 2017

First Posted (Actual)

September 20, 2017

Study Record Updates

Last Update Posted (Actual)

March 28, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P-BCMA-101-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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