Universal Chimeric Antigen Receptor-modified AT19 Cells for CD19+ Relapsed/Refractory Hematological Malignancies

NCT04796688 | Unknown Phase 1

• 1 other identifier: Universal AT19 cells
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of universal chimeric antigen receptor-modified AT19 cells in patients with relapsed or refractory hematological malignancies.

Conditions

Acute Lymphoblastic Leukemia; Chronic Lymphoblastic Leukemia; B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-related Adverse Events

  Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).

  within 2 years after infusion

Secondary Outcomes (5)

• Overall response rate(ORR) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.

  within 2 years after infusion

• Complete response rate(CRR) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.

  within 2 years after infusion

• Progress-free survival(PFS) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.

  2 years after infusion

• Duration of Response(DOR) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.

  2 years after infusion

• Overall survival(OS) of administering AT19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.

  2 years after infusion

Other Outcomes (1)

• In vivo expansion and survival of AT19 cells

  2 years after infusion

Study Arms (1)

Fludarabine + Cyclophosphamide + AT19 cells

EXPERIMENTAL

Patients will received lymphodepletion with fludarabine (30 mg/kg) and cyclophosphamide (300 mg/kg) on days -5, -4, and -3, followed by the infusions of AT19 cells on day 0-2. The study will be divided into three groups: B-ALL, B-CLL, and B-cell lymphoma. Doses of 0.5×10\^7, 1.0×10\^7, and 2.0×10\^7 CAR+ T cells (with an allowance of ±20%) will be tested in each group in the 3+3 dose-escalation study. Each dose group has 3 patients. If no DLT emerges in the group, then the next group uses the subsequent higher dose. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level.The maximum dose could be extended.

Drug: Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells

Interventions

Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells DRUG

fludarabine 30 mg/kg on day -5, -4, and -3; cyclophosphamide 300 mg/kg on day -5, -4, and -3; CAR-NK-CD19 Cells on day 0.

Fludarabine + Cyclophosphamide + AT19 cells

Eligibility Criteria

• Age: 14 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 14-78 years old (including 14 and 78 years old).
• Clinical diagnosis of CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia and lymphoma.
• Refractory/Relapsed B-cell malignancies:
• A. Refractory/relapsed B-cell lymphoblastic leukemia, meeting one of the following criteria:
• i. Recurrence within 6 months after first remission. ii. Primary refractory disease which cannot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.
• iii. Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.
• iv. Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.
• B. Refractory/relapsed B-cell lymphoma, meeting 1 of the first 4 items plus item 5: i. Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
• ii. Achieved CR after standard chemotherapy, but relapsed within 6 months. iii. 2 or more relapses after CR. iv. Not suitable for HSCT, or abandon HSCT due to various restrictions, or relapse after HSCT.
• v. Subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy with anthracyclines.
• Having a measurable or evaluable lesion:
• A. Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.
• B. Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.
• The toxicity related to previous treatments had returned to \< 1 level at enrollment (except for low grade toxicity such as alopecia).
• Patients have good main organs functions:

You may not qualify if:

• Central nervous system is involved in leukemia and lymphoma.
• Known HIV positive patients.
• CNS diseases, such as epilepsy, cerebral ischemia / hemorrhage, dementia, cerebellar diseases or any CNS related autoimmune diseases.
• NYHA class III or higher cardiac failure, or with malignant arrhythmia.
• Myocardial infarction, angioplasty or stent placement, unstable angina or other clinically significant heart history within 12 months before enrollment.
• Patients who need immediate treatment to control tumor progression or relieve tumor burden.
• Active autoimmune diseases requiring systemic immunosuppressive therapy.
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before enrollment.
• Severe immediate hypersensitivity to any drug to be used in this study.
• Women who are pregnant or breastfeeding.
• Other unsuitable conditions in the researchers' opinion.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Chengdu USino Technology Biology Co., Ltd: collaborator

Study Sites (2)

Union Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Union Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell

Interventions

fludarabine; Cyclophosphamide

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; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Heng Mei, M.D., Ph.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei, M.D., Ph.D

CONTACT

027-8572600; hmei@hust.edu.cn

Chenggong Li

CONTACT

18868112136; chenggongli@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proferssor, Cheif Doctor

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 15, 2021
• Study Start: March 10, 2021
• Primary Completion: March 10, 2023
• Study Completion: March 10, 2024
• Last Updated: March 15, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)