JV-213 Autologous CD79b-Targeting CAR-T Cell Therapy in Treating Adults with Relapsed or Refractory B-Cell Lymphomas
This phase I clinical trial tests the safety, side effects, and best dose of anti-CD79b chimeric antigen receptor (CAR) T cells (JV-213) to treat adults with B-cell lymphomas that have come back after treatment (relapsed) or that have not responded to previous treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers.
Inclusion Criteria
- DOSE ESCALATION COHORT: Eligible patients will include those with r/r B-cell lymphoma including LBCL (diffuse large B-cell lymphoma [DLBCL], high-grade B-cell lymphoma [HGBCL], LBCL transformed from indolent lymphoma, and primary mediastinal large B-cell lymphoma [PMBCL]), FL, marginal zone lymphoma, and mantle cell lymphoma (MCL) and other indolent B-cell lymphomas including low-grade B-cell lymphoma, lymphoplasmacytic lymphoma, and nodular lymphocyte predominant Hodgkin lymphoma after at least 2 prior systemic therapies and Burkitt lymphoma after at least 1 prior systemic therapy.
- DOSE EXPANSION COHORT: Patients with r/r LBCL (DLBCL, HGBCL, LBCL transformed from indolent lymphoma, and PMBCL) and FL grade 3B will be eligible. If LBCL patients received CD19 CAR cell therapy as part of first line therapy, then they may be eligible after 1 prior systemic therapy.
- Received at least 2 prior lines of therapy, including anti-CD20 antibody and anthracycline therapy for LBCL, anti-CD20 antibody and alkylating agent or lenalidomide therapy for FL, antiCD20 antibody and alkylating agent or lenalidomide or BTK inhibitor therapy for marginal zone lymphoma, and anti-CD20 antibody and alkylating agent or BTK inhibitor therapy for MCL. Patients with Burkitt lymphoma may be eligible after 1 line of prior therapy including anti-CD20 antibody and anthracycline therapy. Patients with CD20 negative tumor at initial diagnosis or intolerant to anti-CD20 antibody therapy are not required to receive prior anti-CD20 antibody therapy.
- Patients who have received prior CD19 CAR cell therapy using FMC63 antibody for targeting CD19 are eligible and must be at least 6 weeks post CAR infusion and have < 5% of peripheral blood T cells expressing the prior CAR by flow cytometry assessment.
- >= 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- At least one measurable lesion per the Lugano 2014 Classification.
- At least two weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic anti-cancer therapy prior to leukapheresis.
- Toxicities due to prior therapy must be stable and recovered to =< grade 1 (except for clinically non-significant toxicities such as alopecia).
- Absolute neutrophil count of >= 1.0 x 10^9 /L.
- Absolute lymphocyte count of >= 0.1 x 10^9 /L.
- Platelet count of >= 75 x 10^9 /L.
- Creatinine clearance (as estimated by Cockcroft Gault) >= 45 mL/min.
- Serum alanine transaminase (ALT) / aspartate transaminase (AST) =< 5 times the upper limit of normal (ULN).
- Total bilirubin =< 2 mg/dL, except in patients with Gilbert's syndrome.
- Cardiac ejection fraction >= 45% with no evidence of clinically significant pericardial effusion.
- Baseline oxygen saturation >= 92% on room air.
- Women of childbearing potential must have a negative serum or urine pregnancy test (women who have had hysterectomy and women who are over the age of 45 years and have not had a menstrual period for at least 1 year are not considered to be of childbearing potential).
Exclusion Criteria
- Active central nervous system (CNS) lymphoma including patients with detectable cerebrospinal fluid malignant cells or brain metastases. Patients with prior CNS lymphoma that has been effectively treated will be eligible if treatment was completed at least one year prior to enrolment and there is no evidence of disease on magnetic resonance imaging (MRI) with gadolinium contrast at the time of screening.
- Any CAR cell therapy using non-FMC63 antibody.
- History of Richter’s transformation of chronic lymphocytic leukemia.
- Autologous stem cell transplantation within 6 weeks.
- Allogeneic stem cell transplantation within 3 months or active graft versus host disease.
- Active autoimmune disease (e.g. Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus) requiring systemic immunosuppression/systemic disease modifying agents within the last 1 year or inflammatory disease (including graft versus host disease) requiring systemic immunosuppressive therapy. Physiological replacement of corticosteroids of up to 7.5 mg of prednisone or equivalent per day, and topical and inhaled corticosteroids are permitted.
- History of any form of primary immunodeficiency that in the opinion of the investigator may affect efficacy of the CAR-T product.
- History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
- History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 2 years and treated with curative intent. Patients with a prior history of malignancy whose natural history or treatment (e.g. hormonal therapy) does not have the potential to interfere with either the safety or efficacy assessment of the investigational regimen in the opinion of the investigator may be included.
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis or localized skin infections are permitted if responding to active treatment and after consultation with the principal investigator.
- Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B virus surface antigen [HBsAg] positive) or hepatitis C virus (anti-hepatitis C virus [HCV] positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
- History or presence of CNS disorders such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
- Patients with cardiac atrial or cardiac ventricular lymphoma involvement.
- Requirement for urgent therapy due to tumor mass effect such as bowel obstruction or blood vessel compression.
- Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
- Live vaccine =< 6 weeks prior to planned start of conditioning regimen.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the conditioning chemotherapy on the fetus or infant.
- Females of childbearing potential and males of child fathering potential who are not willing to practice two methods of birth control from the time of consent through 6 months after infusion of the study drug.
- In the investigator’s judgment, the patient is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
Additional locations may be listed on ClinicalTrials.gov for NCT05773040.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVE:
I. To determine the safety and identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of anti-CD79b CAR T cells (JV-213) in patients with relapsed/refractory (r/r) B-cell lymphomas.
SECONDARY OBJECTIVE:
I. To determine the efficacy in adults with r/r large b-cell lymphoma (LBCL) and follicular lymphoma (FL) grade 3B treated at the MTD or RP2D of JV-213.
EXPLORATORY OBJECTIVES:
I. To assess the cellular kinetics and pharmacodynamic effects of JV-213 anti-CD79b CAR T-cell product.
II. To evaluate biomarkers associated with response, resistance, and toxicity after administration of JV-213 in blood and tumor samples.
OUTLINE: This is a dose-escalation study of JV-213, followed by a dose-expansion study.
Patients undergo leukapheresis and receive cyclophosphamide intravenously (IV), over 60 minutes, and fludarabine IV, over 30 minutes, on day -5 to -3 and JV-213 IV, in under 60 minutes, on day 0. Patients undergo blood sample collection and positron emission tomography/computed tomography (PET/CT) throughout the trial. Patients may also undergo bone marrow biopsy and aspirate at screening and follow up.
After completion of study treatment, patients are followed up at week 2, 3, 4, month 2, every 3 months up to 24 months then yearly for up to 15 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorSattva S. Neelapu
- Primary ID2022-0938
- Secondary IDsNCI-2023-02055
- ClinicalTrials.gov IDNCT05773040