Clinical trial NCT04609241: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Relapsed and/or Refractory Acute Lymphoblastic Leukemia
Relapsed and/or Refractory B-cell Non-Hodgkin's Lymphoma
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2020-10-30
Enrollment: 72
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

* Only For B-ALL

  1. No gender or age limit
  2. Histologically confirmed diagnosis of CD69b+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1);
  3. Relapsed or refractory CD123+ AML (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 in bone marrow is \> 5% (by morphology), and/or \> 0.01% (by flowcytometry);
  5. 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

  1. No gender or age limit;
  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):

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  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
* For both B-ALL and B-NHL

  1. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, 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 indoorair 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 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after CD79b targeted CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after CD79b targeted CAR T-cells infusion
Secondary outcomes:
measure: Acute Lymphoblastic Leukemia (ALL), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: ALL, Overall survival（OS）
timeFrame: Up to 2 years after CD79b CAR-T cells infusion
measure: ALL, Event-free survival (EFS)
timeFrame: Up to 2 years after CD79b CAR-T cells infusion
measure: B-cell Non-Hodgkin's Lymphoma（B-NHL）, Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: B-NHL, Overall survival（OS）
timeFrame: Up to 2 years after CD79b CAR-T cells infusion
measure: B-NHL, Event-free survival (EFS)
timeFrame: Up to 2 years after CD79b CAR-T cells infusion
measure: Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30)
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Activities of Daily Living (ADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Instrumental Activities of Daily Living (IADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Hospital Anxiety and Depression Scale (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: