A Study of CD20/CD22 Targeted CAR T-cell Therapy for Relapsed or Refractory Lymphoid Malignancies

NCT04283006 | Recruiting Early Phase 1 DMC

• 1 other identifier: CD20/CD22-ZhejiangU
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

A Study of CD20/CD22 Targeted CAR T-cell Therapy for Relapsed or Refractory Lymphoid Malignancies.

Conditions

Relapsed and Refractory; Lymphoid Hematological Malignancies

Keywords

lymphoid hematological malignancies; CAR T-cell therapy; CD20/CD22

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 CD20/CD22 targeted 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 CD20/CD22 targeted CAR T-cells infusion

Secondary Outcomes (6)

• B-cell acute lymphocytic leukemia (B-ALL), MRD negative overall response rate (MRD- ORR)

  3 months

• B-ALL, Event-free survival (EFS)

  Month 6, 12, 18 and 24

• B-ALL, Overall response rate (ORR)

  Month 6, 12, 18 and 24

• B-ALL, Overall survival (OS)

  Month 6, 12, 18 and 24

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

  weeks 4, 12, months 6, 12, 18 and 24

Study Arms (1)

Administration of CD20/CD22 dual Targeted CAR T-cells

EXPERIMENTAL

A dose levels of 3-5\*10E6/kg are administrated for each subject.

Drug: CD20/CD22 dual Targeted CAR T-cells

Interventions

CD20/CD22 dual Targeted CAR T-cells DRUG

Each subject receive CD20/CD22 dual Targeted CAR T-cells by intravenous infusion

Also known as: CD20/CD22 dual Targeted CAR T-cells injection

Administration of CD20/CD22 dual Targeted CAR T-cells

Eligibility Criteria

• Age: 3 Years - 70 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 and \<70 years old;
• Histologically confirmed diagnosis of CD19+ 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 following conditions):
• CR not achieved after standardized chemotherapy;
• CR achieved following the first induction, but CR duration is ≤ 12 months;
• Ineffective after first or multiple remedial treatments;
• or more recurrences;
• The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is \>5% (morphology) and/or \>1% (Flow cytometry);
• 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 and \<70 years old;
• Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2016, including DLBCL(NOS), follicular lymphoma, Chronic lymphoblastic leukemia/small lymphoblastic lymphoma transforms DLBCL, PMBCL and high grade B cell lymphoma;
• Relapsed or refractory DLBCL (meeting one of the following conditions):
• No remission or recurrence after receiving second-line or above second-line chemotherapy;
• Primary drug resistance;
• Recurrence after autologous hematopoietic stem cell transplantation;

You may not qualify if:

• patients with extramedullary lesions, except those with CNSL (CNS-1) under effective control (for ALL patients only);
• Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);
• Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (for ALL patients only);
• Patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;
• Extensive involvement of gastrointestinal lymphoma (for NHL patients only);
• Radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;
• Have a history of allergy to any of the components in the cell products;
• Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
• According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency;
• Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
• Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
• Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
• Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis).
• Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;

Sponsors & Collaborators

• He Huang: 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

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

He Huang, MD

CONTACT

86-13605714822; hehuangyu@126.com

Yongxian Hu, MD

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: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: February 25, 2020
• Study Start: May 23, 2018
• Primary Completion: May 23, 2023
• Study Completion (Estimated): May 23, 2028
• Last Updated: August 21, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)