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

NCT03288493 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: P-BCMA-101-001
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 16

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.

Conditions

Multiple Myeloma

Keywords

CAR-T cells

Outcome Measures

Primary Outcomes (5)

• Phase 1: Assess the Safety of P-BCMA-101

  Incidence and severity of treatment-emergent adverse events

  Baseline through Day 28

• Phase 1: Maximum Tolerated Dose of P-BCMA-101

  Rate of dose limiting toxicities (DLT)

  Baseline through Day 28

• Phase 2: Assess the Safety of P-BCMA-101

  Incidence and severity of treatment-emergent adverse events

  Baseline through 24 months

• 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

• 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 Outcomes (16)

• Phase 1:Assess the Safety of P-BCMA-101

  Baseline through Month 24

• Phase 1:Assess the Feasibility P-BCMA-101

  Baseline through Month 24

• Phase 1: Anti-myeloma Effect of P-BCMA-101 (ORR)

  Baseline through Month 24

• Phase 1: Anti-myeloma Effect of P-BCMA-101 (TTR)

  Baseline through Month 24

• Phase 1: Anti-myeloma Effect of P-BCMA-101 (DOR)

  Baseline through Month 24

Study Arms (8)

Phase 1: P-BCMA-101 CAR-T cells

EXPERIMENTAL

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; Drug: Rimiducid

Phase 1 P-BCMA-101 CAR-T cells (Cohort A)

EXPERIMENTAL

Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.

Biological: P-BCMA-101 CAR-T cells; Drug: Rimiducid

Phase 1 P-BCMA-101 CAR-T cells (Cohort B)

EXPERIMENTAL

Single dose given across three intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.

Biological: P-BCMA-101 CAR-T cells; Drug: Rimiducid

Phase 1 P-BCMA-101 CAR-T cells (Cohort C)

EXPERIMENTAL

Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.

Biological: P-BCMA-101 CAR-T cells; Drug: Rimiducid

Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R)

EXPERIMENTAL

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; Drug: Rimiducid

Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP)

EXPERIMENTAL

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; Drug: Rimiducid

Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT)

EXPERIMENTAL

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; Drug: Rimiducid

Phase 2: P-BCMA-101 CAR-T Cells

EXPERIMENTAL

CAR-T cells administered via intravenous infusion as a total dose

Biological: P-BCMA-101 CAR-T cells; Drug: Rimiducid

Interventions

P-BCMA-101 CAR-T cells BIOLOGICAL

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.

Phase 1 P-BCMA-101 CAR-T cells (Cohort A); Phase 1 P-BCMA-101 CAR-T cells (Cohort B); Phase 1 P-BCMA-101 CAR-T cells (Cohort C); Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R); Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT); Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP); Phase 1: P-BCMA-101 CAR-T cells; Phase 2: P-BCMA-101 CAR-T Cells

Rimiducid DRUG

Rimiducid (safety switch activator) may be administered as indicated.

Phase 1 P-BCMA-101 CAR-T cells (Cohort A); Phase 1 P-BCMA-101 CAR-T cells (Cohort B); Phase 1 P-BCMA-101 CAR-T cells (Cohort C); Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R); Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT); Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP); Phase 1: P-BCMA-101 CAR-T cells; Phase 2: P-BCMA-101 CAR-T Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (16)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of California Davis

Davis, California, 95618, United States

Location

University of California San Diego

San Diego, California, 92093, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Wayne State - Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.

  PMID: 31215818 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Rajesh Belani, MD, Vice President Clinical Development
• Organization: Poseida Therapeutics

rbelani@poseida.com

858-779-3100

Study Officials

• Rajesh Belani, M.D.

  Sponsor Executive Medical Director

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1: open label, 3 + 3 design of dose-escalating cohorts Phase 2: open label, administered as a total dose

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 20, 2017
• Study Start: September 20, 2017
• Primary Completion: April 27, 2022
• Study Completion: April 27, 2022
• Last Updated: March 28, 2024
• Results First Posted: June 22, 2023

Record last verified: 2024-03

Locations

US (16)