A Study of CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Central Nervous System Hematological Malignancies

NCT04532203 | Recruiting Early Phase 1 DMC

• 1 other identifier: CNSL-ZhejiangU
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

A Study of CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Central Nervous System Hematological Malignancies

Conditions

Acute Lymphoblastic Leukemia; Non-Hodgkin's Lymphoma

Keywords

Acute Lymphoblastic Leukemia; Non-Hodgkin's Lymphoma; CAR T-cell therapy

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 (9)

• 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 (1)

Administration of CAR T-cells

EXPERIMENTAL

Dose escalation follows the standard 3+3 doseescalation design. A total of 3 dose levels are set for subjects.

Drug: CAR-T cells; Procedure: Ommaya Reservoir

Interventions

CAR-T cells DRUG

Each subject receive CAR T-cells by intravenous infusion

Also known as: CAR-T cells injection

Administration of CAR T-cells

Ommaya Reservoir PROCEDURE

Surgical catheter placement into the fourth ventricle of the brain

Administration of CAR T-cells

Eligibility Criteria

• Age: 3 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 3-70 years;
• Histologically confirmed diagnosis of B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
• Relapsed or refractory CD19+ B-ALL (meeting one of the followingconditions):
• CR not achieved after standardized chemotherapy;
• CR achieved following the first induction, but CR duration isless than 12 months;
• Ineffectively after first or multiple remedial treatments;
• or more relapses;
• The number of primordial cells (lymphoblast and prolymphocyte)in bone marrow is\>5% (by morphology), and/or \>1% (by flowcytometry);
• Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
• Male or female aged 18-75 years;
• Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHOClassification Criteria for Lymphoma (2016);
• Relapsed or refractory B-NHL (meeting one of the followingconditions):
• No response or relapse after second-line or abovechemotherapy regimens;
• Primary drug resistance;
• Relapse after auto-HSCT;

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 urinarytractinfectionand bacterial pharyngitis);
• Active infection of hepatitis B virus or hepatitis C virus;
• Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;
• 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,orbilirubin\>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 ofpatients or interfere with the results of study.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital，College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 31, 2020
• Study Start: November 1, 2020
• Primary Completion: November 1, 2023
• Study Completion (Estimated): November 1, 2026
• Last Updated: October 26, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)