P-BCMA-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Multiple Myeloma

Multiple Myeloma Clinical Trial

— MM  

Official title:

Open-Label, Multicenter, Phase 1 Study to Assess the Safety of P-BCMA-ALLO1 in Subjects With Relapsed / Refractory Multiple Myeloma (MM)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04960579
• Other study ID #: P-BCMA-ALLO1-001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 5, 2022
• Est. completion date: December 2039

Study information

• Verified date: June 2024
• Source: Poseida Therapeutics, Inc.
• Contact: Angie Schinkel
• Phone: 858-779-3103
• Email: clinicaltrials[@]poseida.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 doses. 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 to guide selection of Recommended Phase 2 Dose (RP2D).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 231
• Est. completion date: December 2039
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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'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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• P-BCMA-ALLO1 CAR-T cells
Allogeneic BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy

Drug:
• Rimiducid
Safety switch activator

Locations

Country	Name	City	State
United States	Sarah Cannon Research Institute - St. David's South Austin Medical Center	Austin	Texas
United States	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Wayne State - Karmanos Cancer Institute	Detroit	Michigan
United States	Houston Methodist Research Institute	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Oklahoma, Health Sciences Center	Oklahoma City	Oklahoma
United States	Advocate Aurora Health	Park Ridge	Illinois
United States	Sarah Cannon Research Institute - Methodist Healthcare	San Antonio	Texas
United States	University of California San Diego	San Diego	California
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Poseida Therapeutics, Inc.	Roche-Genentech

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Part 1: Assess the safety and maximum tolerated dose (MTD) of P-BCMA-ALLO1 based on dose limiting toxicities (DLT)	Rate of dose limiting toxicities (DLT)	Baseline through Day 28
Primary	Phase 1 Part 2: Assess the safety and tolerability of P-BCMA-ALLO1 when administered as a fixed dose of cells.	Frequency and severity of adverse events, including cytokine release syndrome.	Baseline through 36 months
Primary	Phase 1b: The effect of cell dose and study arm to guide selection of Recommended Phase 2 Dose (RP2D).	Incidence and severity of cytokine release syndrome (CRS) events graded using American Society for Transplantation and Cellular Therapy (ASTCT) criteria (Lee, 2019).	Baseline through 36 months
Secondary	The safety of P-BCMA-ALLO1	Incidence and severity of treatment-emergent adverse events	Baseline through 15 years
Secondary	The anti-myeloma effect of P-BCMA-ALLO1 (ORR) in Phase 1 Parts 1 and 2	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 15 years
Secondary	The anti-myeloma effect of P-BCMA-ALLO1 (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 15 years
Secondary	The anti-Myeloma effect of P-BCMA-ALLO1 (DOR)	According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Duration of Response - Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease	Baseline through 15 years
Secondary	The anti-Myeloma effect of P-BCMA-ALLO1 (PFS)	According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Progression Free Survival (PFS) - Time from P-BCMA-ALLO1 treatment to progressive disease	Baseline through 15 years
Secondary	The anti-Myeloma effect of P-BCMA-ALLO1 (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-ALLO1	Baseline through 15 years