Description:
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
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
CD79b-001
- NCT ID:
NCT04609241
Conditions
- Relapsed and/or Refractory Acute Lymphoblastic Leukemia
- Relapsed and/or Refractory B-cell Non-Hodgkin's Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
CD79b CAR-T Cells | | Administration of CD79b CAR-T Cell |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Administration of CD79b CAR-T Cell | Experimental | | |
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):
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | N/A |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose-limiting toxicity (DLT) |
Time Frame: | Baseline up to 28 days after CD79b targeted CAR T-cells infusion |
Safety Issue: | |
Description: | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
Secondary Outcome Measures
Measure: | Acute Lymphoblastic Leukemia (ALL), Overall response rate (ORR) |
Time Frame: | At Month 1, 3, 6, 12, 18 and 24 |
Safety Issue: | |
Description: | Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24 |
Measure: | ALL, Overall survival(OS) |
Time Frame: | Up to 2 years after CD79b CAR-T cells infusion |
Safety Issue: | |
Description: | From the first infusion of CD79b CAR-T cells to death or the last visit |
Measure: | ALL, Event-free survival (EFS) |
Time Frame: | Up to 2 years after CD79b CAR-T cells infusion |
Safety Issue: | |
Description: | From the first infusion of CD79b CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit |
Measure: | B-cell Non-Hodgkin's Lymphoma(B-NHL), Overall response rate (ORR) |
Time Frame: | At Month 1, 3, 6, 12, 18 and 24 |
Safety Issue: | |
Description: | Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24 |
Measure: | B-NHL, Overall survival(OS) |
Time Frame: | Up to 2 years after CD79b CAR-T cells infusion |
Safety Issue: | |
Description: | From the first infusion of CD79b CAR-T cells to death or the last visit |
Measure: | B-NHL, Event-free survival (EFS) |
Time Frame: | Up to 2 years after CD79b CAR-T cells infusion |
Safety Issue: | |
Description: | From the first infusion of CD79b CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit |
Measure: | Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30) |
Time Frame: | At Baseline, Month 1, 3, 6, 9 and 12 |
Safety Issue: | |
Description: | Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12 |
Measure: | Activities of Daily Living (ADL) score |
Time Frame: | At Baseline, Month 1, 3, 6, 9 and 12 |
Safety Issue: | |
Description: | Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12 |
Measure: | Instrumental Activities of Daily Living (IADL) score |
Time Frame: | At Baseline, Month 1, 3, 6, 9 and 12 |
Safety Issue: | |
Description: | Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12 |
Measure: | Hospital Anxiety and Depression Scale (HADS) score |
Time Frame: | At Baseline, Month 1, 3, 6, 9 and 12 |
Safety Issue: | |
Description: | Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12 |
Details
Phase: | Early Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Zhejiang University |
Last Updated
October 30, 2020