Clinical trial NCT04603872: CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Hematological Malignancies
Official title: Clinical Trial for the Safety and Efficacy of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Multiple Myeloma in Relapse
Multiple Myeloma, Refractory
Acute Lymphoblastic Leukemia, in Relapse
Acute Lymphocytic Leukaemia Refractory
Non-Hodgkin's Lymphoma, Relapsed
Non-Hodgkin's Lymphoma Refractory
Keywords: Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma
Multiple Myeloma
CAR T-cell therapy
Dasatinib
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2020-10-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Study of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.

Detailed description: This is a double-arm, single-center study. This study is indicated for relapsed and/or refractory B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin's lymphoma and multiple myeloma, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 120 patients will be enrolled for this trial. Primary objective is to explore the safety.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2);
2. Relapsed or refractory B cell hematological malignancies (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;
   5. Relapse after hematopoietic stem cell transplantation;
   6. Extramedullary leisions which were ineffective to radiotherapy or chemotherapy;
3. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
5. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
6. Estimated survival time ≥ 12 weeks;
7. ECOG performance status 0 to 2;
8. Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion.
9. Patients 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 toscreening, except for the patients recently or currently receiving in haledsteroids;
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 CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after 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 CAR-T cells infusion
measure: B-ALL, Event-free survival (EFS)
timeFrame: Up to 2 years after 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: Multiple myeloma (MM), Overall response rate (ORR)
timeFrame: At Day 28
measure: MM, Overall survival (OS)
timeFrame: At Month 6, 12, 24
measure: Quality of life
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 Hospital of Zhejiang Medical Colleage Zhejiang University
state: Zhejiang
Study officials:
References: