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

Patrocinadores

Patrocinador principal: Precision BioSciences, Inc.

Fuente Precision BioSciences, Inc.
Resumen breve

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.

Descripción detallada

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.

Estado general Recruiting
Fecha de inicio April 30, 2020
Fecha de Terminación May 2021
Fecha de finalización primaria May 2021
Fase Phase 1/Phase 2
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Maximum Tolerated Dose (MTD) of PBCAR269A Day 1 - Day 28
Resultado secundario
Medida Periodo de tiempo
Number of Participants with Dose Limiting Toxicity(ies) 1 year
Objective Response Rate of Patients 1 year
Inscripción 48
Condición
Intervención

Tipo de intervención: Genetic

Nombre de intervención: PBCAR269A

Descripción: Allogeneic anti-BCMA CAR T-cell

Tipo de intervención: Drug

Nombre de intervención: Fludarabine

Descripción: Fludarabine is used for lymphodepletion.

Tipo de intervención: Drug

Nombre de intervención: Cyclophosphamide

Descripción: Cyclophosphamide is used for lymphodepletion.

Elegibilidad

Criterios:

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.

Género: All

Edad mínima: 18 Years

Edad máxima: N/A

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
Chris R Heery, MD Study Chair Precision BioSciences, Inc.
Contacto general

Apellido: Clinical Precision BioSciences, Inc.

Teléfono: 919-314-5512

Email: [email protected]

Ubicación
Instalaciones: Estado: Contacto: Investigador:
City of Hope | Duarte, California, 91010, United States Recruiting Maung Myo Htut, MD Maung Myo Htut, MD Principal Investigator
University of California San Francisco | San Francisco, California, 94115, United States Not yet recruiting Nina Shah, MD Principal Investigator
Dana Farber Cancer Institute | Boston, Massachusetts, 02215, United States Not yet recruiting Omar Nadeem, MD Principal Investigator
Columbia University Irving Medical Center | New York, New York, 10032, United States Recruiting Ran Reshef, MD Principal Investigator
MD Anderson | Houston, Texas, 77030, United States Not yet recruiting Krina Patel, MD Principal Investigator
Ubicacion Paises

United States

Fecha de verificación

July 2020

Fiesta responsable

Tipo: Sponsor

Tiene acceso ampliado No
Condición Examinar
Número de brazos 3
Grupo de brazo

Etiqueta: PBCAR269A at Dose Level 1

Tipo: Experimental

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

Etiqueta: PBCAR269A at Dose Level 2

Tipo: Experimental

Descripción: 2 × 10^6 CAR T cells/kg body weight.

Etiqueta: PBCAR269A at Dose Level 3

Tipo: Experimental

Descripción: 6 × 10^6 CAR T cells/kg body weight.

Información de diseño del estudio

Asignación: Non-Randomized

Modelo de intervención: Sequential Assignment

Descripción del modelo de intervención: In Phase I, 3 escalating dose groups will be enrolled and treated sequentially, with the possibility of a single de-escalation. Within each dose group, at least 3 and at most 6 study participants will be treated with a single dose of PBCAR269A using a standard 3 + 3 design. The starting dose of PBCAR269A will be 6 x 105 CAR T cells/kg body weight. Subsequent dose groups will be treated with escalating doses to a maximum dose of 6 x 106 CAR T cells/kg. In the absence of DLTs, the dose will be increased using a fixed-dose scheme.

Propósito primario: Treatment

Enmascaramiento: None (Open Label)

Fuente: ClinicalTrials.gov