A Study of Murine CD19 CAR-T Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04532281

Collaborator

Yake Biotechnology Ltd. (Industry)

120

Enrollment

Location

Arm

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Study of Murine CD19 CAR-T Cells Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia Non-Hodgkin Lymphoma of Soft Tissue	Drug: Murine CD19 CAR-T cells	Early Phase 1

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 number of 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Administration of Murine CD19 CAR T-cells	Drug: Murine CD19 CAR-T cells Each subject receive murine CD19 CAR T-cells by intravenous infusion Other Names: Murine CD19 CAR-T cells injection

Arm

Intervention/Treatment

Experimental: Administration of Murine CD19 CAR T-cells

Drug: Murine CD19 CAR-T cells

Each subject receive murine CD19 CAR T-cells by intravenous infusion

Other Names:

Murine CD19 CAR-T cells injection

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity (DLT) [Baseline up to 28 days after murine CD19 targeted CAR T-cells infusion]
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years after murine CD19 targeted CAR T-cells infusion]
Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR) [At Month 1, 3, 6, 12, 18 and 24]
Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
B-ALL, Overall survival (OS) [Up to 2 years after murine CD19 CAR-T cells infusion]
From the first infusion of murine CD19 CAR-T cells to death or the last visit
B-ALL, Event-free survival (EFS) [Up to 2 years after murine CD19 CAR-T cells infusion]
From the first infusion of murine CD19 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit
B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) [At Week 4, 12, and Month 6, 12, 18, 24]
Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria
B-NHL, disease control rate (DCR) [At Week 12 and Month 6, 12, 18, 24]
Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria
Quality of life [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12
Activities of Daily Living (ADL) score [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment using Activities of Daily Living (ADL) scale at Baseline, Month 1, 3, 6, 9 and 12
Instrumental Activities of Daily Living (IADL) score [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment of Instrumental Activities of Daily Living (IADL) scale at Baseline, Month 1, 3, 6, 9 and 12
Hospital Anxiety and Depression Scale (HADS) score [At Baseline, Month 1, 3, 6, 9 and 12]
Assessment using Hospital Anxiety and Depression Scale (HADS) at Baseline, Month 1, 3, 6, 9 and 12

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inclusion criteria only for B-ALL:

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:

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 tractinfectionand 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 in haled 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.