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

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04532268
• Other study ID #: hCD19-001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: August 23, 2020
• Est. completion date: August 23, 2026

Study information

• Verified date: August 2020
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: August 23, 2026
• Est. primary completion date: August 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 75 Years

Eligibility

Inclusion Criteria:

• Inclusion criteria only for B-ALL:

1. Male or female aged 3-70 years;

2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);

3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

1. CR not achieved after standardized chemotherapy;

2. CR achieved following the first induction, but CR duration is less than 12 months;

3. Ineffectively after first or multiple remedial treatments;

4. 2 or more relapses;

4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (by morphology), and/or >1% (by flow cytometry);

5. 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:

1. Male or female aged 18-75 years;

2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);

3. Relapsed or refractory B-NHL (meeting one of the following conditions):

1. No response or relapse after second-line or above chemotherapy regimens;

2. Primary drug resistance;

3. Relapse after auto-HSCT;

4. At least one assessable tumor lesion per Lugano 2014 criteria;

• Common inclusion criteria for B-ALL and B-NHL:

1. Total bilirubin = 51 umol/L, ALT and AST = 3 times of upper limit of normal, creatinine = 176.8 umol/L;

2. Echocardiogram shows left ventricular ejection fraction (LVEF) = 50%;

3. No active infection in the lungs, blood oxygen saturation in indoor air is = 92%;

4. Estimated survival time = 3 months;

5. ECOG performance status 0 to 2;

6. 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:

1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;

2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;

3. Pregnant (or lactating) women;

4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);

5. Active infection of hepatitis B virus or hepatitis C virus;

6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;

7. Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;

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 of patients or interfere with the results of study.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-hodgkin Lymphoma,B Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
China	The First Affiliated Hospital,College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Yake Biotechnology Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after humanized CD19 targeted CAR T-cells infusion
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after humanized CD19 targeted CAR T-cells infusion
Secondary	B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
Secondary	B-ALL, Overall survival (OS)	From the first infusion of humanized CD19 CAR-T cells to death or the last visit	Up to 2 years after humanized CD19 CAR-T cells infusion
Secondary	B-ALL, Event-free survival (EFS)	From the first infusion of humanized 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	Up to 2 years after humanized CD19 CAR-T cells infusion
Secondary	B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)	Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria	At Week 4, 12, and Month 6, 12, 18, 24
Secondary	B-NHL, disease control rate (DCR)	Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria	At Week 12 and Month 6, 12, 18, 24
Secondary	Quality of life	Assessment of Quality of life using Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	IADL score	Assessment of IADL score at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	ADL score	Assessment of ADL score at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	HADS score	Assessment of Hospital Anxiety and Depression Scale (HADS) score at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12