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Recruiting Early Phase 1

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

NCT06446128 · tracked via the Priya Life Science China tracker
Phase
Early Phase 1
Started
2024-05-07
Last updated
2025-08-21

Condition(s) studied

Non-Hodgkin Lymphoma, B-cell

Investigational drug(s) / intervention(s)

CD19/CD20/BCMA CAR T cells

CD19/CD20/BCMA CAR T cells: 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

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.

Primary outcome measure(s)

  • Dose-limiting toxicity(DLT) — Day0-Day28
    Safety
  • Maximum tolerated dose (MTD) — Day0-Day28
    Tolerability

Trial sites (1)

FacilityCityRegionStatus
Mengchao Cancer Hospital Shanghai Shanghai Municipality Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06446128 on ClinicalTrials.gov ↗ ← All trials in China