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

Zhejiang University

Status and phase: Enrolling; Early Phase 1

Conditions: Acute Lymphocytic Leukaemia Refractory; Multiple Myeloma in Relapse; Non-Hodgkin's Lymphoma, Relapsed; Non-Hodgkin's Lymphoma Refractory; Multiple Myeloma, Refractory; Acute Lymphoblastic Leukemia, in Relapse

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04603872

DASA001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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120 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

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

Administration of CD19/BCMA Targeted CAR T-cells

Experimental group

Description:

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

Treatment:

Drug: CD19/BCMA Targeted CAR T-cells