Study Stopped
Study was terminated due to lack of sufficient therapeutic effect
A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A, With or Without Nirogacestat, in Study Participants With Relapsed/Refractory Multiple Myeloma
A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion Study to Evaluate the Safety and Clinical Activity of PBCAR269A, With or Without Nirogacestat, in Study Participants With Relapsed/Refractory Multiple Myeloma
1 other identifier
interventional
48
1 country
5
Brief Summary
This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR269A, with or without nirogacestat, in adults with r/r MM. Study subjects in Cohort A will receive PBCAR269A and study subjects in Cohort B will receive PBCAR269A and nirogacestat. At each dose level, study subjects in Cohort A and Cohort B will receive the same dose of PBCAR269A. In Cohort B, all study subjects will follow the same dosing regimen of nirogacestat. This study was terminated prior to beginning of Phase II due to lack of sufficient therapeutic effect
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2020
Typical duration for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 12, 2019
CompletedFirst Posted
Study publicly available on registry
November 21, 2019
CompletedStudy Start
First participant enrolled
April 30, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 19, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
October 19, 2022
CompletedSeptember 21, 2023
September 1, 2023
2.5 years
November 12, 2019
September 18, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose (MTD) of PBCAR269A
To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.
Day 1 - Day 28
Secondary Outcomes (2)
Number of Participants with Dose Limiting Toxicity(ies)
1 year
Objective Response Rate of Patients
1 year
Study Arms (6)
PBCAR269A at Dose Level 1 (Cohort A)
EXPERIMENTALThe starting dose of PBCAR269A will be 6 x 10\^5 CAR T cells/kg body weight.
PBCAR269A at Dose Level 2
EXPERIMENTAL2 × 10\^6 CAR T cells/kg body weight.
PBCAR269A at Dose Level 3
EXPERIMENTAL6 × 10\^6 CAR T cells/kg body weight.
PBCAR269A at Dose Level 2 (Cohort B)
EXPERIMENTAL2 × 10\^6 CAR T cells/kg body weight.
PBCAR269A at Dose Level 1 (Cohort B)
EXPERIMENTAL6 x 10\^5 CAR T cells/kg body weight.
PBCAR269A at Dose Level 3 (Cohort B)
EXPERIMENTAL6 × 10\^6 CAR T cells/kg body weight.
Interventions
Allogeneic anti-BCMA CAR T-cell
Fludarabine is used for lymphodepletion.
Cyclophosphamide is used for lymphodepletion.
Allogeneic anti-BCMA CAR T-cell
Eligibility Criteria
You may qualify if:
- Diagnosis of MM with relapsed and/or refractory disease according to the IMWG criteria.
- Measurable disease at Screening including at least 1 of the criteria below. Note: Study participants with immunoglobulin (Ig) A myeloma in whom serum protein electrophoresis is deemed unreliable due to comigration of normal serum proteins with the paraprotein in the beta region may be considered eligible provided total serum IgA level is \>400 mg/dL.
- Serum myeloma (M)-protein ≥0.5 g/dL or, urine M-protein \>200 mg/24 hour.
- Serum free light chain \>10mg/dL with abnormal kappa:lambda ratio.
- Imaging consistent plasmacytoma and the presence of any clonal plasma cells in peripheral blood or bone marrow.
- Study participants must be refractory to 2 prior MM treatment regimens including an immunomodulatory imide drug and a protease inhibitor prior to entering the study. Study participants must have recovered or stabilized to Grade ≤2 from any AEs experienced during prior treatment with the exception of neuropathy. Prior therapy requirements are as follows:
- Undergone ≥1 complete cycle of treatment for each regimen, unless progressive disease was the best response to the regimen.
- Must have received an immunomodulatory agent, a proteasome inhibitor, and an anti- CD38 antibody.
- Study participants who are not candidates for ≥1 of the above treatments may still be considered eligible.
- Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
- Estimated glomerular filtration rate \>30 mL/min/1.73 m2. A 24-hour urine collection for creatinine clearance may be used at the investigator's discretion.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both
- ≤3 times of upper limit of normal, unless there is suspected disease in the liver, in which case, no limit is set provided serum bilirubin is within eligibility criterion.
- Total bilirubin \<2.0 mg/dL, except in study participants with Gilbert's syndrome.
- +8 more criteria
You may not qualify if:
- Study participant has clinically significant organ involvement by amyloid protein.
- Study participant has plasma cell leukemia, Waldenstrom's macroglobulinemia, or POEMS syndrome.
- History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months of starting study treatment.
- History or presence of clinically relevant central nervous system (CNS) pathology.
- Active uncontrolled fungal, bacterial, viral, protozoal, or other infection.
- Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).
- History of human immunodeficiency virus (HIV) infection.
- Active hepatitis B or hepatitis C confirmed by polymerase chain reaction (PCR). Study participant positive for inactive hepatitis B will be allowed to enroll if on prophylactic treatment.
- History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Abnormal findings during the Screening Period or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the study participant's safety.
- History of genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
- Study participants with active hemolytic anemia.
- Study participant has received autologous stem cell transplant within 12 weeks of Screening or an allogeneic stem cell transplant within 6 months of starting study treatment. Study participants who have received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of GvHD.
- Study participants with second malignancies in addition to MM if the second malignancy has required treatment within the last 3 years or is not in complete remission, with the exception of non-metastatic basal cell or squamous cell skin carcinoma.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
City of Hope
Duarte, California, 91010, United States
University of California San Francisco
San Francisco, California, 94115, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Columbia University Irving Medical Center
New York, New York, 10032, United States
MD Anderson
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Monika Vainorius, MD
Precision BioSciences, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 12, 2019
First Posted
November 21, 2019
Study Start
April 30, 2020
Primary Completion
October 19, 2022
Study Completion
October 19, 2022
Last Updated
September 21, 2023
Record last verified: 2023-09