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

NCT04603872 | Recruiting Early Phase 1 DMC

• 1 other identifier: DASA001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Adverse events assessed according to NCI-CTCAE v5.0 criteria

  Baseline up to 28 days after CAR T-cells infusion

• 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 Outcomes (11)

• B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)

  At Month 1, 3, 6, 12, 18 and 24

• B-ALL, Overall survival (OS)

  Up to 2 years after CAR-T cells infusion

• B-ALL, Event-free survival (EFS)

  Up to 2 years after CAR-T cells infusion

• B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)

  At Week 4, 12, and Month 6, 12, 18, 24

• B-NHL, disease control rate (DCR)

  At Week 12 and Month 6, 12, 18, 24

Study Arms (2)

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

EXPERIMENTAL

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

Administration of CD19/BCMA Targeted CAR T-cells

EXPERIMENTAL

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

Drug: CD19/BCMA Targeted CAR T-cells

Interventions

CD19/BCMA Targeted CAR T-cells and dasatinib DRUG

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

Also known as: Administration of CD19/BCMA Targeted CAR T-cells and dasatinib

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

CD19/BCMA Targeted CAR T-cells DRUG

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

Also known as: CD19/BCMA Targeted CAR T-cells infusion

Administration of CD19/BCMA Targeted CAR T-cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang University: lead
• Yake Biotechnology Ltd.: collaborator

Study Sites (1)

The First Hospital of Zhejiang Medical Colleage Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Recurrence

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Lymphatic Diseases; Lymphoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Central Study Contacts

He Huang, PhD

CONTACT

86-13605714822; hehuangyu@126.com

Yongxian Hu, PhD

CONTACT

86-15957162012; huyongxian2000@aliyun.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: October 27, 2020
• Study Start: November 1, 2020
• Primary Completion: November 1, 2023
• Study Completion (Estimated): November 1, 2026
• Last Updated: October 28, 2020

Record last verified: 2020-10

Locations

CN (1)