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

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03288493
• Other study ID #: P-BCMA-101-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 20, 2017
• Est. completion date: April 27, 2022

Study information

• Verified date: March 2024
• Source: Poseida Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 105
• Est. completion date: April 27, 2022
• Est. primary completion date: April 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	University of Chicago	Chicago	Illinois
United States	University of California Davis	Davis	California
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Wayne State - Karmanos Cancer Institute	Detroit	Michigan
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of California San Diego	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Poseida Therapeutics, Inc.	California Institute for Regenerative Medicine (CIRM)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Assess the Safety of P-BCMA-101	Incidence and severity of treatment-emergent adverse events	Baseline through Day 28
Primary	Phase 1: Maximum Tolerated Dose of P-BCMA-101	Rate of dose limiting toxicities (DLT)	Baseline through Day 28
Primary	Phase 2: Assess the Safety of P-BCMA-101	Incidence and severity of treatment-emergent adverse events	Baseline through 24 months
Primary	Phase 2: Assess the Efficacy of P-BCMA-101 (ORR)	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
Primary	Phase 2: Assess the Efficacy of P-BCMA-101 (DOR)	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	Phase 1:Assess the Safety of P-BCMA-101	Incidence and severity of treatment-emergent adverse events	Baseline through Month 24
Secondary	Phase 1:Assess the Feasibility P-BCMA-101	Ability to generate protocol-prescribed doses of P-BCMA-101.	Baseline through Month 24
Secondary	Phase 1: Anti-myeloma Effect of P-BCMA-101 (ORR)	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
Secondary	Phase 1: Anti-myeloma Effect of P-BCMA-101 (TTR)	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
Secondary	Phase 1: Anti-myeloma Effect of P-BCMA-101 (DOR)	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
Secondary	Phase 1: Anti-myeloma Effect of P-BCMA-101 (PFS)	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
Secondary	Phase 1: Anti-myeloma Effect of P-BCMA-101 (OS)	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
Secondary	Phase 1: The Effect of Cell Dose to Guide Selection of Doses for Further Assessment in Phase 2/3 Studies	Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)	Baseline through Month 24
Secondary	Phase 2: Incidence and Severity of Cytokine Release Syndrome (CRS)	Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)	Baseline through Month 24
Secondary	Phase 2: Evaluate Efficacy Endpoints (IL-6)	Rate of IL-6 antagonist	Baseline through Month 24
Secondary	Phase 2: Evaluate Efficacy Endpoints (C)	Corticosteroid Use	Baseline through Month 24
Secondary	Phase 2: Evaluate Efficacy Endpoints (R)	Rimiducid Use	Baseline through Month 24
Secondary	Phase 2: Evaluate Efficacy Endpoints (OS)	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
Secondary	Phase 2: Evaluate Efficacy Endpoints (PFS)	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
Secondary	Phase 2: Evaluate Efficacy Endpoints (TTR)	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
Secondary	Phase 2: Evaluate Efficacy Endpoints (MRD)	Minimum residual disease negative rate	Baseline through Month 24