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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 : November 18, 2019
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Poseida Therapeutics, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: P-BCMA-101 CAR-T cells Drug: Rimiducid Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
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, single dose
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 20, 2017
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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 2 P-BCMA-101 CAR-T cells (Cohort A)
Single dose given across two intravenous infusion pf 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 2 P-BCMA-101 CAR-T cells (Cohort B)
Single dose given across three 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.




Primary Outcome Measures :
  1. Phase 1: Assess the Safety of P-BCMA-101 [ Time Frame: Baseline through Day 28 ]
    Incidence and severity of treatment-emergent adverse events

  2. Phase 1: Maximum tolerated dose of P-BCMA-101 [ Time Frame: Baseline through Day 28 ]
    Rate of dose limiting toxicities (DLT)

  3. Phase 2: Assess the safety of P-BCMA-101 [ Time Frame: Baseline through 24 months ]
    Incidence and severity of treatment-emergent adverse events

  4. 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).


  5. 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.



Secondary Outcome Measures :
  1. Phase 1:Assess the safety of P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
    Incidence and severity of treatment-emergent adverse events

  2. Phase 1:Assess the feasibility P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
    Ability to generate protocol-proscribed doses of P-BCMA-101.

  3. 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).


  4. 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.


  5. 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.


  6. 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.


  7. 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.


  8. 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)

  9. 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)

  10. Phase 2: Evaluate Efficacy Endpoints (IL-6) [ Time Frame: Baseline through Month 24 ]
    Rate of IL-6 antagonist

  11. Phase 2: Evaluate Efficacy Endpoints (C) [ Time Frame: Baseline through Month 24 ]
    Corticosteroid Use

  12. Phase 2: Evaluate Efficacy Endpoints (R) [ Time Frame: Baseline through Month 24 ]
    Rimiducid Use

  13. 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.


  14. 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.


  15. 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.


  16. Phase 2: Evaluate Efficacy Endpoints (MRD) [ Time Frame: Baseline through Month 24 ]
    Minimum residual disease negative rate



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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.

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): NCT03288493


Contacts
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Contact: Angie Schinkel 858 779 3103 clinicaltrials@poseida.com

Locations
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United States, California
University of California San Diego Recruiting
San Diego, California, United States, 92093
University of California San Francisco Not yet recruiting
San Francisco, California, United States, 94143
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas Cancer Center Not yet recruiting
Westwood, Kansas, United States, 66205
United States, Maryland
University of Maryland Greenebaum Comprehensive Cancer Center Not yet recruiting
Baltimore, Maryland, United States, 21201
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21231
United States, Michigan
Wayne State - Karmanos Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48201
United States, New Jersey
John Theurer Cancer Center Not yet recruiting
Hackensack, New Jersey, United States, 07601
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute at Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute Not yet recruiting
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Poseida Therapeutics, Inc.
California Institute for Regenerative Medicine (CIRM)
Investigators
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Study Director: Matthew A Spear, M.D. Sponsor Chief Medical Officer

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Responsible Party: Poseida Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03288493     History of Changes
Other Study ID Numbers: P-BCMA-101-001
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: November 18, 2019
Last Verified: November 2019

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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 Poseida Therapeutics, Inc.:
CAR-T cells
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