CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

Official title

Clinical Trial for the Safety and Efficacy of Murine CD79b CAR-T Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

Overview

A study of CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory 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 Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 72 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.

Interventions

• Drug CD79b CAR-T Cells
  Each subject receive CD79b CAR-Tcells by intravenous infusion

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Baseline up to 28 days after CD79b targeted CAR T-cells infusion]
• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: Up to 2 years after CD79b targeted CAR T-cells infusion]

Secondary outcome measures (10)

• Acute Lymphoblastic Leukemia (ALL), Overall response rate (ORR) [Time frame: At Month 1, 3, 6, 12, 18 and 24]
• ALL, Overall survival（OS） [Time frame: Up to 2 years after CD79b CAR-T cells infusion]
• ALL, Event-free survival (EFS) [Time frame: Up to 2 years after CD79b CAR-T cells infusion]
• B-cell Non-Hodgkin's Lymphoma（B-NHL）, Overall response rate (ORR) [Time frame: At Month 1, 3, 6, 12, 18 and 24]
• B-NHL, Overall survival（OS） [Time frame: Up to 2 years after CD79b CAR-T cells infusion]
• B-NHL, Event-free survival (EFS) [Time frame: Up to 2 years after CD79b CAR-T cells infusion]
• Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30) [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]
• Activities of Daily Living (ADL) score [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]
• Instrumental Activities of Daily Living (IADL) score [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]
• Hospital Anxiety and Depression Scale (HADS) score [Time frame: At Baseline, Month 1, 3, 6, 9 and 12]

Eligibility criteria

Inclusion criteria

• Only For B-ALL

• No gender or age limit
• Histologically confirmed diagnosis of CD69b+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);
• Relapsed or refractory CD123+ AML (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 in bone marrow is > 5% (by morphology), and/or > 0.01% (by flowcytometry);
• Philadelphia chromosome negative(Ph-) subjects; Ph+ subjects who cannot tolerate tyrosine kinase inhibitor (TKI) treatment or who do not respond to two kinds of TKI treatment;
• Only For B-NHL

• No gender or age limit;
• 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):

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• 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
• For both B-ALL and B-NHL

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

Exclusion criteria

• 1\. History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagicdiseases; 2. Electrocardiogram shows prolonged QT interval, severe heart diseasessuch as severe arrhythmia in the past; 3. Pregnant (or lactating) women; 4. Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis); 5. Active infection of hepatitis B virus or hepatitis C virus; 6. Previously treated with any CAR-T cell product or other genetically modified T cell therapies; 7. Insufficient amplification capacity in response to CD3 / CD28 co-stimulus signal (<5 times) 8. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; 9. Other uncontrolled diseases that were not suitable for this trial; 10. Patients with HIV infection; 11. Any situations that the investigator believes may increase the risk ofpatients 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

Identifiers

NCT: NCT04609241 · CD79b-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗