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

Multiple Myeloma in Relapse Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04603872
• Other study ID #: DASA001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 1, 2020
• Est. completion date: November 1, 2026

Study information

• Verified date: October 2020
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: November 1, 2026
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia, in Relapse
• Acute Lymphocytic Leukaemia Refractory
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Multiple Myeloma in Relapse
• Multiple Myeloma, Refractory
• Neoplasms, Plasma Cell
• Non-Hodgkin's Lymphoma Refractory
• Non-Hodgkin's Lymphoma, Relapsed
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrence

Intervention

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.
• CD19/BCMA Targeted CAR T-cells
Each subject receive CS1 Targeted CAR T-cells by intravenous infusion.

Locations

Country	Name	City	State
China	The First Hospital of Zhejiang Medical Colleage Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Yake Biotechnology Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after CAR T-cells infusion
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after CAR T-cells infusion
Secondary	B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)	Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
Secondary	B-ALL, Overall survival (OS)	From the first infusion of CAR-T cells to death or the last visit	Up to 2 years after CAR-T cells infusion
Secondary	B-ALL, Event-free survival (EFS)	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	Up to 2 years after CAR-T cells infusion
Secondary	B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)	Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria	At Week 4, 12, and Month 6, 12, 18, 24
Secondary	B-NHL, disease control rate (DCR)	Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria	At Week 12 and Month 6, 12, 18, 24
Secondary	Multiple myeloma (MM), Overall response rate (ORR)	Assessment of ORR at Day 28	At Day 28
Secondary	MM, Overall survival (OS)	Assessment of OS at Month 6, 12, 24	At Month 6, 12, 24
Secondary	Quality of life	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	Activities of Daily Living (ADL) score	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	Instrumental Activities of Daily Living (IADL) score	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	At Baseline, Month 1, 3, 6, 9 and 12
Secondary	Hospital Anxiety and Depression Scale (HADS) score	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	At Baseline, Month 1, 3, 6, 9 and 12