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

Phase 1

Terminated

• Conditions: Multiple Myeloma
• Interventions: Biological: P-BCMA-101 CAR-T cells; Drug: Rimiducid

• Registration Number: NCT03288493
• Lead Sponsor: Poseida Therapeutics, Inc.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-09-13
• Study First Submitted QC: 2017-09-18
• Study Start: 2017-09-20
• Study First Posted: 2017-09-20
• Primary Completion: 2022-04-27
• Study Completion: 2022-04-27
• Results First Submitted: 2023-04-25
• Results First Submitted QC: 2023-05-26
• Results First Posted: 2023-06-22
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-26
• Last Update Posted: 2024-03-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 105

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

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1 P-BCMA-101 CAR-T cells (Cohort A)	Rimiducid	Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
Phase 1: P-BCMA-101 CAR-T cells	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.
Phase 1: P-BCMA-101 CAR-T cells	Rimiducid	Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells (Cohort A)	P-BCMA-101 CAR-T cells	Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells (Cohort B)	Rimiducid	Single dose given across three intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells (Cohort C)	P-BCMA-101 CAR-T cells	Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells (Cohort C)	Rimiducid	Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R)	P-BCMA-101 CAR-T cells	Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R)	Rimiducid	Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP)	P-BCMA-101 CAR-T cells	Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before apheresis. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells (Cohort B)	P-BCMA-101 CAR-T cells	Single dose given across three intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP)	Rimiducid	Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before apheresis. Rimiducid may be administered as indicated.
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT)	P-BCMA-101 CAR-T cells	Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
Phase 2: P-BCMA-101 CAR-T Cells	P-BCMA-101 CAR-T cells	CAR-T cells administered via intravenous infusion as a total dose
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT)	Rimiducid	Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
Phase 2: P-BCMA-101 CAR-T Cells	Rimiducid	CAR-T cells administered via intravenous infusion as a total dose

Primary Outcome Measures

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

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

Trial Locations

Locations (16)

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

University of California San Diego; 🇺🇸 San Diego, California, United States

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

University of California Davis; 🇺🇸 Davis, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Wayne State - Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

University of Kansas Cancer Center; 🇺🇸 Westwood, Kansas, United States

University of Maryland Greenebaum Comprehensive Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

John Theurer Cancer Center; 🇺🇸 Hackensack, New Jersey, United States

Sarah Cannon Research Institute at Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States