Clinical trial NCT04532268: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Acute Lymphoblastic Leukemia
Non-hodgkin Lymphoma,B Cell
Keywords: Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma
CAR T-cell therapy
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2020-08-31
Enrollment: 72
Sex: ALL
Minimum age (years): 3
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after humanized CD19 targeted CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after humanized CD19 targeted CAR T-cells infusion
Secondary outcomes:
measure: B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: B-ALL, Overall survival (OS)
timeFrame: Up to 2 years after humanized CD19 CAR-T cells infusion
measure: B-ALL, Event-free survival (EFS)
timeFrame: Up to 2 years after humanized CD19 CAR-T cells infusion
measure: B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)
timeFrame: At Week 4, 12, and Month 6, 12, 18, 24
measure: B-NHL, disease control rate (DCR)
timeFrame: At Week 12 and Month 6, 12, 18, 24
measure: Quality of life
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: IADL score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: ADL score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: HADS score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital，College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: