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

NCT ID: NCT03288493

Last Updated: 2024-03-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-20
• Study Completion Date: 2022-04-27

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

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

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

Group Type: EXPERIMENTAL

P-BCMA-101 CAR-T cells

Intervention Type: 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.

Rimiducid

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: BIOLOGICAL

Rimiducid

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

Intervention Type: DRUG

Eligibility 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.
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

California Institute for Regenerative Medicine (CIRM)

OTHER

Sponsor Role: collaborator

Poseida Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rajesh Belani, M.D.

Role: STUDY_DIRECTOR

Sponsor Executive Medical Director

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

University of California Davis

Davis, California, United States

University of California San Diego

San Diego, California, United States

University of California San Francisco

San Francisco, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

University of Chicago

Chicago, Illinois, 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

Wayne State - Karmanos Cancer Institute

Detroit, Michigan, United States

John Theurer Cancer Center

Hackensack, New Jersey, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31215818 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P-BCMA-101-001

Identifier Type: -

Identifier Source: org_study_id