A Dose Escalating Study of CD19/CD22/BCMA CAR-T Therapy in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)

Trial Title: A Dose Escalating Study of CD19/CD22/BCMA CAR-T Therapy in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)

NCT ID: NCT06446128

Condition: Non-Hodgkin Lymphoma, B-cell

Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell

Conditions: Keywords:
B cell non-hodgkin lymphoma
CAR-T
CD19
CD22
BCMA

Study type: Interventional

Study phase: Early Phase 1

Overall status: Active, not recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: CD19/CD20/BCMA CAR T cells
Description: Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CD19/CD20/BCMA CAR T cells. Cyclophosphamide and fludarabine will be given from day-5 to day-3 before the infusion for lymphodepletion. On day0 subjects will receive one dose treatment with CD19/CD20/BCMA CAR T cells by intravenous (IV) injection
Arm group label: CD19/CD20/BCMA CAR T therapy

Summary: This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous chimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA in patients with relapsed or refractory B cell non-Hodgkin lymphoma.

Detailed description: This is a single arm, open-label, dose escalation investigator initiated (IIT) study, the primary objective is to evaluate the safety and tolerability of CD19/CD22/BCMA CAR-T therapy in patients with B cell non-Hodgkin lymphoma, and determine the maximum tolerated dose (MTD). For the secondary objectives, pharmacokinetics(PK), survival of CAR-T cells in vivo, pharmacodynamics (PD) and efficacy in R/R B cell NHL will be evaluated. This study flow comprises of a screening phase( ≤28 days prior to apheresis), apheresis phase (occur upon enrollment, ≤10 days prior to infusion), lymphodepletion phase (from Day -5 to Day -3) ,infusion of CD19/CD22/BCMA CAR-T cells on Day0, DLT assessments phase from Day1 to Day 28 and post-treatment follow-up phase (Day 29 and up to end of the study).

Criteria for eligibility:
Criteria:
Key Inclusion Criteria: - Patients who are diagnosed with relapsed/refractory B cell non-Hodgkin lymphoma , especially - Diffuse Large B Cell Lymphoma, not other specified (DLBCL,NOS), - Primary Mediastinal Large B Cell Lymphoma (PMBCL) - Transformation Follicular Lymphoma (TFL) - High grade B-cell lymphoma(HGBCL) - High grade B-cell lymphoma (HGBCL) with MYC(myelocytomatosis oncogene) and BCL2(B-cell lymphoma2) /BCL6 (B-cell lymphoma6) rearrangement - Refractory diseases are defined as one of the following - No response to last line of therapy: i. Progressive disease (PD) as best response to most recent therapy regimen; ii. Stable disease (SD) as best response to most recent therapy regimen - Not candidate for autologous stem cell transplant (ASCT) or refractory post-ASCT: i. Disease progression (PD) or relapsed ≤12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy - Individuals must have received adequate prior therapy including at a minimum: - anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and - an anthracycline containing chemotherapy regimen - Immunohistochemical staining shows at least two of B cell surface receptor antigen CD19,CD20, BCMA are positive(including weak, medium and strong positive) - At least one measurable lesion during the screening based on the recommendation for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma. - Life expectancy ≥ 12 weeks - Eastern cooperative oncology group (ECOG) performance status of 0 or 1 - Adequate renal, hepatic, pulmonary and cardiac function defined as: - Renal function: Serum creatinine ≤ 1.5 upper limit of normal(ULN), or eGFR ≥ 60 mL/min/1.73m2 [eGFR(estimated glomerular filtration rate)=186×age^-0.203×SCr^-1.154（mg/dl）,female×0.742] - Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 ULN and ii: total bilirubin ≤ 2 ULN, except in individuals with Gilbert syndrome (in Gilbert's syndrome patients, those with total bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN can be enrolled).iii: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN Pulmonary: Have the minimum level of pulmonary reserve, defined as ≤ CTCAE (Common Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen saturation)≥ 91% on room air - Cardiac: left ventricular ejection fraction (LVEF) ≥50% determined by echocardiogram(ECG) or multigated acquisition scan (MUGA) - Adequate bone marrow function, define as: - absolute neutrophil count (ANC) ≥1 ×10^9/L - absolute lymphocyte count (ALC)≥ 0.5 ×10^9/L - Platelets ≥50 ×109/L； - Hemoglobulin ≥80 g/L; patients with bone marrow involvement can be enrolled if globulin>60 g/L - Female of child-bearing age and male participants must agree to use effective contraceptive methods until no CAR-T cells can be detected by PCR(polymerase chain reaction) test. Key Exclusion Criteria: - Individuals who have antiCD45 or antiCD3 therapy - Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of primary or secondary CNS (central nervous system) lymphoma, cerebrospinal fluid malignant cells or brain metastases - Presence or history of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement - History of allogeneic stem cell transplantation - Any of the following situations: • HBsAg/ HBeAg positive; HBeAb/HBcAb positive and HBV(hepatitis B virus) DNA copies above the lower test limit; - HCV(hepatitis C virus) RNA positive - HIV(human immunodeficiency virus) positive or treponema pallidum positive - Presence of active or life-threatening fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. - Individuals presence of unstable angina or myocardial infarction within 6 months of screening, or other severe/uncontrolled diseases during the screening (eg. Unstable or uncompensated respiratory, cardiac, hepatic or renal disease) - Presence of uncontrolled arrhythmia with treatment - Pregnancy or breastfeeding women Other protocol defined inclusion/exclusion criteria may apply.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Mengchao Cancer Hospital

Address:
City: Shanghai
Zip: 201800
Country: China

Start date: April 1, 2024

Completion date: July 1, 2025

Lead sponsor:
Agency: Shanghai Cell Therapy Group Co.,Ltd
Agency class: Industry

Source: Shanghai Cell Therapy Group Co.,Ltd

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06446128