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

Early Phase 1

Recruiting

• Conditions: Acute Lymphoblastic Leukemia; Non-Hodgkin Lymphoma of Soft Tissue
• Interventions: Drug: Murine CD19 CAR-T cells

• Registration Number: NCT04532281
• Lead Sponsor: Zhejiang University

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-08-20
• Study First Submitted QC: 2020-08-25
• Study First Posted: 2020-08-31
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-22
• Last Update Posted: 2020-10-26
• Study Start: 2020-11-01
• Primary Completion: 2023-11-01
• Study Completion: 2026-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Inclusion criteria only for B-ALL:

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

  2. 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;

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

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

  2. 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;

  3. 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 tractinfectionand 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 in haled 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of Murine CD19 CAR T-cells	Murine CD19 CAR-T cells	-

Primary Outcome Measures

Name	Time	Method
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 \[Safety and Tolerability\]
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

Secondary Outcome Measures

Name	Time	Method
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-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
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
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
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

Trial Locations

Locations (1)

The First Affiliated Hospital，College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China