A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A in Study Participants With Relapsed/Refractory Multiple Myeloma

Study Purpose

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 in adults with r/r MM.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Diagnosis of MM with relapsed and/or refractory disease according to the IMWG criteria. 2. 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. 1. Serum myeloma (M)-protein ≥0.5 g/dL or, urine M-protein >200 mg/24 hour. 2. Serum free light chain >10mg/dL with abnormal kappa:lambda ratio. 3. Imaging consistent plasmacytoma and the presence of any clonal plasma cells in peripheral blood or bone marrow. 3. 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: 1. Undergone ≥1 complete cycle of treatment for each regimen, unless progressive disease was the best response to the regimen. 2. Must have received an immunomodulatory agent, a proteasome inhibitor, and an anti- CD38 antibody. 3. Study participants who are not candidates for ≥1 of the above treatments may still be considered eligible. 4. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 5. Has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as: 1. Estimated glomerular filtration rate >60 mL/min/1.73 m2. A 24-hour urine collection for creatinine clearance may be used at the investigator's discretion. 2. 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. 3. Total bilirubin <2.0 mg/dL, except in study participants with Gilbert's syndrome. 4. Platelet count >50,000/μL (platelet transfusions acceptable); neutrophils >750/μL. 5. Left ventricular ejection fraction (LVEF) >45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan performed within 1 month before starting lymphodepleting chemotherapy. ECHO results performed within 6 months before Screening and at least 28 days after the last cancer treatment may be acceptable if the study participant has not received any treatment with cardiotoxicity risks. 6. No clinically significant evidence of pericardial effusion or pleural effusion based on investigator's opinion. 7. Baseline oxygen saturation >92% on room air. 8. Pulmonary function tests including forced expiratory volume at 1 sec, forced vital capacity, total lung capacity, diffusion capacity of lung for carbon monoxide ≥50% of predicted values. Study participant characteristics. 6. All study participants must be willing to practice birth control and refrain from donating sperm or oocytes from the time of enrollment in this study through 3 months after receiving the study treatment. 7. Women of childbearing potential (WOCBP) must test negative for pregnancy at Screening because of the potentially harmful effects of the preparative chemotherapy to the fetus. WOCBP are defined as any women who are not postmenopausal or who have not had a hysterectomy. Postmenopausal is defined as women over the age of 55 who have not had a menstrual period for ≥1 year. 8. Capable of giving signed informed consent.

Exclusion Criteria:

1. Study participant has clinically significant organ involvement by amyloid protein. 2. Study participant has plasma cell leukemia, Waldenstrom's macroglobulinemia, or POEMS syndrome. 3. 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. 4. History or presence of clinically relevant central nervous system (CNS) pathology. 5. Active uncontrolled fungal, bacterial, viral, protozoal, or other infection. 6. Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease). 7. History of human immunodeficiency virus (HIV) infection. 8. 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. 9. History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening. 10. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 11. 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. 12. History of genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome. 13. Study participants with active hemolytic anemia. 14. 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. 15. 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. 16. Study participant has received systemic biologic agent within 28 days. Participation in non-interventional registries or epidemiological studies is not excluded. 17. Study participant has received live vaccine within 4 weeks before Screening. Non-live virus vaccines are not excluded. 18. Before initiation of lymphodepletion, study participants must have recovered or stabilized to Grade ≤2 from any AEs experienced during prior treatment with the exception of neuropathy. 19. Radiotherapy within 4 weeks before Screening should be discussed with the monitor. 20. Presence of pleural/peritoneal/pericardial catheter. 21. Current use of any anticoagulant or antiplatelet therapy.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04171843
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Precision BioSciences, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Monika Vainorius, MD
Principal Investigator Affiliation Precision BioSciences, Inc.
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Relapsed/Refractory Multiple Myeloma
Additional Details

This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR269A in adults with r/r MM. Before initiating the study treatment PBCAR269A, all study participants will be administered lymphodepletion chemotherapy. The initial lymphodepletion chemotherapy regimen will be composed of fludarabine and cyclophosphamide during the Screening Period. On Day 0 of the Treatment Period, study participants will receive a single intravenous (IV) infusion of PBCAR269A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR269A will be followed in a separate long-term follow-up (LTFU) study for 15 years after exiting this study.

Arms & Interventions

Arms

Experimental: PBCAR269A at Dose Level 1

The starting dose of PBCAR269A will be 6 x 10^5 CAR T cells/kg body weight.

Experimental: PBCAR269A at Dose Level 2

2 × 10^6 CAR T cells/kg body weight.

Experimental: PBCAR269A at Dose Level 3

6 × 10^6 CAR T cells/kg body weight.

Interventions

Genetic: - PBCAR269A

Allogeneic anti-BCMA CAR T-cell

Drug: - Fludarabine

Fludarabine is used for lymphodepletion.

Drug: - Cyclophosphamide

Cyclophosphamide is used for lymphodepletion.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

City of Hope, Duarte, California

Status

Recruiting

Address

City of Hope

Duarte, California, 91010

Site Contact

Maung Myo Htut, MD

clinical@precisionbiosciences.com

919-314-5512

University of California San Francisco, San Francisco, California

Status

Recruiting

Address

University of California San Francisco

San Francisco, California, 94115

Dana Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

New York, New York

Status

Recruiting

Address

Columbia University Irving Medical Center

New York, New York, 10032

MD Anderson, Houston, Texas

Status

Recruiting

Address

MD Anderson

Houston, Texas, 77030