Cord Blood Derived Anti-CD19 CAR-Engineered NK Cells for B Lymphoid Malignancies

NCT04796675 | Unknown Phase 1

• 1 other identifier: CAR-NK-CD19 cells
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of anti-CD19 chimeric antigen receptor(CAR)-modified NK cells(CAR-NK-CD19) in patients with relapsed or refractory hematological malignancies.

Conditions

Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Non Hodgkin's 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 CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.

  within 2 years after infusion

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

  within 2 years after infusion

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

  within 2 years after infusion

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

  within 2 years after infusion

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

  within 2 years after infusion

Other Outcomes (1)

• In vivo expansion and survival of CAR-NK-CD19 cells

  within 2 years after infusion

Study Arms (1)

Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells

EXPERIMENTAL

Patients will received lymphodepletion with fludarabine (30 mg/kg) and cyclophosphamide (300 mg/kg) on day -5, -4, and -3, followed by one infusion of CAR-NK-CD19 cells on day 0. The study will be divided into three groups: Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, and Non Hodgkin's Lymphoma. Doses of 0.01×10\^7, 0.1×10\^7, 1.0×10\^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 dose-limited toxicity (DLT) emerges in the group, then the subsequent higher dose will be used in the next group. 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 + CAR-NK-CD19 Cells

Eligibility Criteria

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

You may qualify if:

• Aged ≥ 18 years;
• Eastern Cooperative Oncology Group score≤ 3;
• Diagnosed as CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia and Non Hodgkin's lymphoma.
• Patients must relapse or be refractory after at least two lines of therapy.
• Patient's main organs functioning well:
• A. Liver function: alanine aminotransferase/aspartate aminotransferase \< 2.5 times the upper limit of normal (ULN) and total bilirubin≤ 1.5 times ULN; B. Renal function: Creatinine clearance rate ≥ 60ml/min. C. Pulmonary function: Indoor oxygen saturation ≥ 95%. D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥50%, no clinically-significant ECG findings.
• Negativity of blood pregnancy test for woman, and participants use effective methods of contraception until last follow-up.
• Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

You may not qualify if:

• Investigators judge the patients with gastrointestinal lymph node and/or central nervous system involvement who may be at high-risk of receiving CAR-NK-CD19 cell treatment.
• Patients with graft-versus-host reaction and need immunosuppressive agents, or patients with autoimmune diseases.
• Systemic steroids are used within 5 days before apheresis.
• Drugs to stimulate the production of bone marrow hematopoietic cells are used within 5 days before apheresis.
• Patients receive cytotoxic chemotherapy or radiotherapy within 21 days before enrollment(Tyrosine kinase inhibitors or other targeted therapies can be used two weeks before lymphodepleting chemotherapy).
• History of epilepsy or other central nervous system diseases.
• Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within five years.
• Known HIV positive patients.
• Patients with active infections, including active replication of hepatitis B or active hepatitis C.
• Patients receive any antitumor treatments within 4 weeks before enrollment, and the toxicity related to previous treatments don't return to \< 1 level at enrollment (except for low grade toxicity such as alopecia).
• Major surgery in the past 4 weeks.
• Non-compliant patients.
• Anticoagulants are being used.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Shanghai Simnova Biotechnology Co.,Ltd.: collaborator

Study Sites (1)

Union Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Related Publications (1)

• Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607.

  PMID: 32023374 BACKGROUND

MeSH Terms

Conditions

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

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Yu Hu

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei

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: April 10, 2021
• Primary Completion: March 10, 2023
• Study Completion: March 10, 2024
• Last Updated: April 8, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)