Clinical trial NCT04960579: P-BCMA-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Multiple Myeloma
Official title: Open-Label, Multicenter, Phase 1 Study to Assess the Safety of P-BCMA-ALLO1 in Subjects With Relapsed / Refractory Multiple Myeloma (MM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Poseida Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Roche-Genentech
First posted: 2021-07-14
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase 1 study comprised of open-label, dose escalation, multiple cohorts of P-BCMA-ALLO1 allogeneic T stem cell memory (Tscm) CAR-T cells in subjects with relapsed / refractory Multiple Myeloma (RRMM).

Detailed description: Phase 1/1b study: Phase 1 Part 1 is a weight-based dose escalation following a 3+3 design of dose-escalating cohorts. Phase 1 Part 2 includes administration at fixed doses. After enrollment, subjects may receive a lymphodepletion therapy regimen before administration of allogeneic CAR-T cells, administered as a single or multiple dose(s). Treated subjects will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated. Phase 1b of the study will undergo further expansion of cohorts/arms from Phase 1 Parts 1 or 2 or an intermediate dose between cohort levels.

Eligibility criteria: Inclusion Criteria:

1. Must have signed written, informed consent.
2. Males or females, ≥18 years of age.
3. Must have a confirmed diagnosis of active MM.
4. Must have measurable MM.
5. Must have relapsed / refractory MM, having received treatment with a proteasome inhibitor, immunomodulatory agent (IMiD), and anti-CD38 therapy.
6. Must be willing to practice birth control from the time of Screening and throughout the first year of the study after P-BCMA-ALLO1 administration.
7. Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 3 days prior to initiating the lymphodepletion therapy regimen (females of childbearing potential).
8. Must be at least 90 days since autologous stem cell transplant, if performed.
9. Must have adequate vital organ function within pre-determined parameters.
10. Must have recovered from toxicities due to prior therapies.
11. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion Criteria:

1. Is pregnant or lactating.
2. Has inadequate venous access.
3. Has active hemolytic anemia, plasma cell leukemia, Waldenstrom\&amp;#39;s macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, or amyloidosis.
4. 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.
5. Has active autoimmune disease.
6. Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy, etc.
7. Has an active systemic infection.
8. Has a history of hepatitis B, hepatitis C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome. Subjects with a history of treated hepatitis C can be enrolled if negative by Hepatitis C PCR on multiple occasions and with medical monitor approval.
9. Is positive for cytomegalovirus (CMV) by PCR, CMV immunoglobulin M (IgM) antibody, or Coronavirus disease 2019 (COVID-19) by PCR.
10. Has New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of myocardial infarction or significant arrhythmia.
11. Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol.
12. Has received prior allogeneic cellular therapy or gene therapy.
13. Has received anti-cancer medications within 2 weeks of the time of initiating conditioning LD therapy.
14. Has received monoclonal antibody therapy within 4 weeks of initiating conditioning LD therapy.
15. Has received immunosuppressive medications within 2 weeks of the time of administration of P-BCMA-ALLO1, and/or expected to require them while on study.
16. Has received systemic corticosteroid therapy within 1 week or 5 half-lives (whichever is shorter) of the administration of P-BCMA-ALLO1 or is expected to require it during the course of the study.
17. Has CNS metastases or symptomatic CNS involvement of their myeloma.
18. Has a history of severe immediate hypersensitivity reaction to any of the agents used in this study.
19. 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.
20. Arms R, RS, RP1, RP1.5 and RP2 Only: a) Has received a live vaccine within the last 28 days of the first administration of agents used in Arm R or RS, b) Has any known hypersensitivity or severe reactions or toxicity to agents used in Arms R or RS.
21. Has received radiation within 1 week of initiating conditioning LD therapy.

Primary outcomes:
measure: Phase 1 Part 1: Assess the safety and maximum tolerated dose (MTD) of P-BCMA-ALLO1 based on dose limiting toxicities (DLT)
timeFrame: Baseline through Day 28
measure: Phase 1 Part 2: Assess the safety and tolerability of P-BCMA-ALLO1 when administered as a fixed dose of cells.
timeFrame: Baseline through 36 months
measure: Phase 1b: The effect of cell dose and study arm to guide selection of Recommended Phase 2 Dose (RP2D).
timeFrame: Baseline through 36 months
Secondary outcomes:
measure: The safety of P-BCMA-ALLO1
timeFrame: Baseline through 15 years
measure: The anti-myeloma effect of P-BCMA-ALLO1 (ORR) in Phase 1 Parts 1 and 2
timeFrame: Baseline through 15 years
measure: The anti-myeloma effect of P-BCMA-ALLO1 (TTR)
timeFrame: Baseline through 15 years
measure: The anti-Myeloma effect of P-BCMA-ALLO1 (DOR)
timeFrame: Baseline through 15 years
measure: The anti-Myeloma effect of P-BCMA-ALLO1 (PFS)
timeFrame: Baseline through 15 years
measure: The anti-Myeloma effect of P-BCMA-ALLO1 (OS)
timeFrame: Baseline through 15 years
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: City of Hope
state: Arizona
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: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Blood Marrow and Transplant Group of Georgia
state: Georgia
city: Chicago
country: United States
facility: City of Hope
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Aurora Health
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Wayne State - Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma, Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Sarah Cannon Research Institute - St. David's South Austin Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: San Antonio
country: United States
facility: Sarah Cannon Research Institute - Methodist Healthcare
state: Texas
Study officials:
affiliation: Vice President, Clinical Development
name: Rajesh Belani, M.D.
role: STUDY_DIRECTOR
References: