CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Hematological Malignancies

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04603872

Collaborator

Yake Biotechnology Ltd. (Industry)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: CD19/BCMA Targeted CAR T-cells and dasatinib Drug: CD19/BCMA Targeted CAR T-cells	Early Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Administration of CD19/BCMA Targeted CAR T-cells and dasatinib Dose levels of CAR-T cells are based on clinical trials of similar foreign products. Meanwhile, dasatinib would be combined as the following regimens: 1) Dasatinib preconditioning CAR-T cells during the manufacturing; 2) Dasatinib for the intervention of cytokine release storm after CAR-T cell infusion; 3) Dasatinib for the intervention of neurotoxicities after CAR-T cell infusion; 4) Dasatinib for the phase of CAR-T cell decreasing.	Drug: CD19/BCMA Targeted CAR T-cells and dasatinib Each subject receive CS1 Targeted CAR T-cells by intravenous infusion, and the dasatinib was combined according to the presumed regimens. Other Names: Administration of CD19/BCMA Targeted CAR T-cells and dasatinib
Experimental: Administration of CD19/BCMA Targeted CAR T-cells Dose levels of CAR-T cells are based on clinical trials of similar foreign products.	Drug: CD19/BCMA Targeted CAR T-cells Each subject receive CS1 Targeted CAR T-cells by intravenous infusion. Other Names: CD19/BCMA Targeted CAR T-cells infusion

Arm

Intervention/Treatment

Experimental: Administration of CD19/BCMA Targeted CAR T-cells and dasatinib

Dose levels of CAR-T cells are based on clinical trials of similar foreign products. Meanwhile, dasatinib would be combined as the following regimens: 1) Dasatinib preconditioning CAR-T cells during the manufacturing; 2) Dasatinib for the intervention of cytokine release storm after CAR-T cell infusion; 3) Dasatinib for the intervention of neurotoxicities after CAR-T cell infusion; 4) Dasatinib for the phase of CAR-T cell decreasing.

Drug: CD19/BCMA Targeted CAR T-cells and dasatinib

Each subject receive CS1 Targeted CAR T-cells by intravenous infusion, and the dasatinib was combined according to the presumed regimens.

Other Names:

Administration of CD19/BCMA Targeted CAR T-cells and dasatinib

Experimental: Administration of CD19/BCMA Targeted CAR T-cells

Dose levels of CAR-T cells are based on clinical trials of similar foreign products.

Drug: CD19/BCMA Targeted CAR T-cells

Each subject receive CS1 Targeted CAR T-cells by intravenous infusion.

Other Names:

CD19/BCMA Targeted CAR T-cells infusion

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicity (DLT) [Baseline up to 28 days after CAR T-cells infusion]
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years after CAR T-cells infusion]
Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

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 CAR-T cells infusion]
From the first infusion of CAR-T cells to death or the last visit
B-ALL, Event-free survival (EFS) [Up to 2 years after CAR-T cells infusion]
From the first infusion of CAR-T cells to the occurrence of any event, including death, relapse orgene relapse, disease progression (any one occurs first), and the last visit
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
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
Multiple myeloma (MM), Overall response rate (ORR) [At Day 28]
Assessment of ORR at Day 28
MM, Overall survival (OS) [At Month 6, 12, 24]
Assessment of OS at Month 6, 12, 24
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 [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
Activities of Daily Living (ADL) score [At Baseline, Month 1, 3, 6, 9 and 12]
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
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 [max score: 56, min score: 14, higher scores mean a worse outcome] 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) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2);
Relapsed or refractory B cell hematological malignancies (meeting one of the following conditions):
CR not achieved after standardized chemotherapy;
CR achieved following the first induction, but CR duration is less than 12 months;
Ineffectively after first or multiple remedial treatments;
2 or more relapses;
Relapse after hematopoietic stem cell transplantation;
Extramedullary leisions which were ineffective to radiotherapy or chemotherapy;
Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
Estimated survival time ≥ 12 weeks;
ECOG performance status 0 to 2;
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.
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:

History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
Pregnant (or lactating) women;
Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
Active infection of hepatitis B virus or hepatitis C virus;
Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
Creatinine >2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin >2.0 mg/dl;
Other uncontrolled diseases that were not suitable for this trial;
Patients with HIV infection;
Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.