Clinical trial NCT03288493: P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: CAR-T cells
Lead sponsor: Poseida Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2017-09-20
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1: open label, 3 + 3 design of dose-escalating cohorts Phase 2: open label, administered as a total dose
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Phase 1: Assess the Safety of P-BCMA-101
timeFrame: Baseline through Day 28
measure: Phase 1: Maximum Tolerated Dose of P-BCMA-101
timeFrame: Baseline through Day 28
measure: Phase 2: Assess the Safety of P-BCMA-101
timeFrame: Baseline through 24 months
measure: Phase 2: Assess the Efficacy of P-BCMA-101 (ORR)
timeFrame: Baseline through 24 months
measure: Phase 2: Assess the Efficacy of P-BCMA-101 (DOR)
timeFrame: Baseline through 24 months
Secondary outcomes:
measure: Phase 1:Assess the Safety of P-BCMA-101
timeFrame: Baseline through Month 24
measure: Phase 1:Assess the Feasibility P-BCMA-101
timeFrame: Baseline through Month 24
measure: Phase 1: Anti-myeloma Effect of P-BCMA-101 (ORR)
timeFrame: Baseline through Month 24
measure: Phase 1: Anti-myeloma Effect of P-BCMA-101 (TTR)
timeFrame: Baseline through Month 24
measure: Phase 1: Anti-myeloma Effect of P-BCMA-101 (DOR)
timeFrame: Baseline through Month 24
measure: Phase 1: Anti-myeloma Effect of P-BCMA-101 (PFS)
timeFrame: Baseline through Month 24
measure: Phase 1: Anti-myeloma Effect of P-BCMA-101 (OS)
timeFrame: Baseline through Month 24
measure: Phase 1: The Effect of Cell Dose to Guide Selection of Doses for Further Assessment in Phase 2/3 Studies
timeFrame: Baseline through Month 24
measure: Phase 2: Incidence and Severity of Cytokine Release Syndrome (CRS)
timeFrame: Baseline through Month 24
measure: Phase 2: Evaluate Efficacy Endpoints (IL-6)
timeFrame: Baseline through Month 24
measure: Phase 2: Evaluate Efficacy Endpoints (C)
timeFrame: Baseline through Month 24
measure: Phase 2: Evaluate Efficacy Endpoints (R)
timeFrame: Baseline through Month 24
measure: Phase 2: Evaluate Efficacy Endpoints (OS)
timeFrame: Baseline through Month 24
measure: Phase 2: Evaluate Efficacy Endpoints (PFS)
timeFrame: Baseline through Month 24
measure: Phase 2: Evaluate Efficacy Endpoints (TTR)
timeFrame: Baseline through Month 24
measure: Phase 2: Evaluate Efficacy Endpoints (MRD)
timeFrame: Baseline through Month 24
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Davis
country: United States
facility: University of California Davis
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Detroit
country: United States
facility: Wayne State - Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: Sponsor Executive Medical Director
name: Rajesh Belani, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.