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

Sponsor
Poseida Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03288493
Collaborator
California Institute for Regenerative Medicine (CIRM) (Other)
220
Enrollment
16
Locations
8
Arms
57.3
Anticipated Duration (Months)
13.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
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. 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 Design

Study Type:
Interventional
Anticipated Enrollment :
220 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, administered as a total dosePhase 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
Official Title:
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)
Actual Study Start Date :
Sep 20, 2017
Anticipated Primary Completion Date :
Dec 31, 2021
Anticipated Study Completion Date :
Jun 30, 2022

Arms and Interventions

ArmIntervention/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.

Outcome Measures

Primary Outcome Measures

  1. Phase 1: Assess the Safety of P-BCMA-101 [Baseline through Day 28]

    Incidence and severity of treatment-emergent adverse events

  2. Phase 1: Maximum tolerated dose of P-BCMA-101 [Baseline through Day 28]

    Rate of dose limiting toxicities (DLT)

  3. Phase 2: Assess the safety of P-BCMA-101 [Baseline through 24 months]

    Incidence and severity of treatment-emergent adverse events

  4. Phase 2: Assess the efficacy of P-BCMA-101 (ORR) [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) [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 [Baseline through Month 24]

    Incidence and severity of treatment-emergent adverse events

  2. Phase 1:Assess the feasibility P-BCMA-101 [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) [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) [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) [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) [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) [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 [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) [Baseline through Month 24]

    Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)

  10. Phase 2: Evaluate Efficacy Endpoints (IL-6) [Baseline through Month 24]

    Rate of IL-6 antagonist

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

    Corticosteroid Use

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

    Rimiducid Use

  13. Phase 2: Evaluate Efficacy Endpoints (OS) [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) [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) [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) [Baseline through Month 24]

    Minimum residual disease negative rate

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Banner MD Anderson Cancer CenterGilbertArizonaUnited States85234
2University of California DavisDavisCaliforniaUnited States95618
3University of California San DiegoSan DiegoCaliforniaUnited States92093
4University of California San FranciscoSan FranciscoCaliforniaUnited States94143
5Colorado Blood Cancer InstituteDenverColoradoUnited States80218
6University of ChicagoChicagoIllinoisUnited States60637
7University of Kansas Cancer CenterWestwoodKansasUnited States66205
8University of Maryland Greenebaum Comprehensive Cancer CenterBaltimoreMarylandUnited States21201
9Johns Hopkins UniversityBaltimoreMarylandUnited States21231
10Wayne State - Karmanos Cancer InstituteDetroitMichiganUnited States48201
11John Theurer Cancer CenterHackensackNew JerseyUnited States07601
12University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104
13Sarah Cannon Research Institute at Tennessee OncologyNashvilleTennesseeUnited States37203
14Vanderbilt University Medical CenterNashvilleTennesseeUnited States37232
15MD Anderson Cancer CenterHoustonTexasUnited States77030
16Swedish Cancer InstituteSeattleWashingtonUnited States98104

Sponsors and Collaborators

  • Poseida Therapeutics, Inc.
  • California Institute for Regenerative Medicine (CIRM)

Investigators

  • Study Director: Matthew A Spear, M.D., Sponsor Chief Medical Officer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Poseida Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT03288493
Other Study ID Numbers:
  • P-BCMA-101-001
First Posted:
Sep 20, 2017
Last Update Posted:
Sep 14, 2021
Last Verified:
Sep 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Poseida Therapeutics, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 14, 2021