A Study of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell ALL and B-cell NHL

Official title

Clinical Trial for the Safety and Efficacy of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

Overview

A Study of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma.

Detailed description

This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia and B-cell non-Hodgkin's lymphoma. The selections of dose levels and the numberof subjects are based on clinical trials of similar foreign products. Two groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.

Interventions

• Drug Humanized CD19 CAR-T cells
  Each subject receive humanized CD19 CAR T-cells by intravenous infusion

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Baseline up to 28 days after humanized CD19 targeted CAR T-cells infusion]
• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: Up to 2 years after humanized CD19 targeted CAR T-cells infusion]

Secondary outcome measures (9)

• B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR) [Time frame: At Month 1, 3, 6, 12, 18 and 24]
• B-ALL, Overall survival (OS) [Time frame: Up to 2 years after humanized CD19 CAR-T cells infusion]
• B-ALL, Event-free survival (EFS) [Time frame: Up to 2 years after humanized CD19 CAR-T cells infusion]
• B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) [Time frame: At Week 4, 12, and Month 6, 12, 18, 24]
• B-NHL, disease control rate (DCR) [Time frame: At Week 12 and Month 6, 12, 18, 24]
• Quality of life [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]
• IADL score [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]
• ADL score [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]
• HADS score [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]

Eligibility criteria

Inclusion criteria

• Inclusion criteria only for B-ALL:

• Male or female aged 3-70 years;
• Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
• Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

• CR not achieved after standardized chemotherapy;
• CR achieved following the first induction, but CR duration is less than 12 months;
• Ineffectively after first or multiple remedial treatments;
• 2 or more relapses;
• The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (by morphology), and/or >1% (by flow cytometry);
• Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
• Inclusion criteria only for B-NHL:

• Male or female aged 18-75 years;
• Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
• Relapsed or refractory B-NHL (meeting one of the following conditions):

• No response or relapse after second-line or above chemotherapy regimens;
• Primary drug resistance;
• Relapse after auto-HSCT;
• At least one assessable tumor lesion per Lugano 2014 criteria;
• Common inclusion criteria for B-ALL and B-NHL:

• Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
• Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
• No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
• Estimated survival time ≥ 3 months;
• ECOG performance status 0 to 2;
• Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion criteria

Subjects with any of the following exclusion criteria were not eligible for this trial:

• History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
• Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• Pregnant (or lactating) women;
• Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
• Active infection of hepatitis B virus or hepatitis C virus;
• Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;
• Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
• Creatinine >2.5mg/dl, or ALT / AST>3 times of normal amounts, or bilirubin>2.0 mg/dl;
• Other uncontrolled diseases that were not suitable for this trial;
• Patients with HIV infection;
• Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital，College of Medicine, Zhejiang University — Hangzhou

Publications

• Zhou L, Fu W, Wu S, Xu K, Qiu L, Xu Y, Yan X, Zhang Q, Zhang M, Wang L, Hong R, Chang AH, Yu J, Fu S, Kong D, Li L, Wang Y, Li Z, Jiang H, Huang J, Liu Z, Su N, Wei G, Hu Y, Huang H. Derivation and validation of a novel score for early prediction of severe CRS after CAR-T therapy in haematological malignancy patients: A multi-centre study. Br J Haematol. 2023 Aug;202(3):517-524. doi: 10.1111/bjh.1 PMID 37192741
• Song F, Hu Y, Zhang Y, Zhang M, Yang T, Wu W, Huang S, Xu H, Chang AH, Huang H, Wei G. Safety and efficacy of autologous and allogeneic humanized CD19-targeted CAR-T cell therapy for patients with relapsed/refractory B-ALL. J Immunother Cancer. 2023 Feb;11(2):e005701. doi: 10.1136/jitc-2022-005701. PMID 36808074

Identifiers

NCT: NCT04532268 · hCD19-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗