Back to results

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

Primary Purpose

Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Non Hodgkin's Lymphoma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells

About this trial

This is an interventional treatment trial for Acute Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Union Hospital, Huazhong University of Science and TechnologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).

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

CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).

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

PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).

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

DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).

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

OS will be assessed from CAR T cell infusion to death or last follow-up (censored).

Full Information

NCT ID

NCT04796675

First Posted

March 10, 2021

Last Updated

April 5, 2021

Sponsor

Wuhan Union Hospital, China

Collaborators

Shanghai Simnova Biotechnology Co.,Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04796675

Brief Title

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

Official Title

Safety and Efficacy of Cord Blood Derived Anti-CD19 CAR-Engineered NK Cells for Relapsed/Refractory B Lymphoid Malignancies: a Single-center, Open-label, Single-arm Clinical Study

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Recruiting

Study Start Date

April 10, 2021 (Anticipated)

Primary Completion Date

March 10, 2023 (Anticipated)

Study Completion Date

March 10, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Wuhan Union Hospital, China

Collaborators

Shanghai Simnova Biotechnology Co.,Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

Detailed Description

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. Cord blood(CB) derived NK cells from healthy donor are the source for production of CAR-NK-CD19 cells. CB derived NK cells are purified and transduced with a retroviral vector encoding the anti-CD19 CAR and interleukin-15. This is an investigational study. The objectives are to evaluate the safety and efficacy of CAR-NK-CD19 cells in patients with CD19+ B-cell malignancies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, Non Hodgkin's Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of Treatment-related Adverse Events

Description

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).

Time Frame

within 2 years after infusion

Secondary Outcome Measure Information:

Title

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

Description

ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).

Time Frame

within 2 years after infusion

Title

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

Description

CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).

Time Frame

within 2 years after infusion

Title

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

Description

PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).

Time Frame

within 2 years after infusion

Title

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

Description

DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).

Time Frame

within 2 years after infusion

Title

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

Description

OS will be assessed from CAR T cell infusion to death or last follow-up (censored).

Time Frame

within 2 years after infusion

Other Pre-specified Outcome Measures:

Title

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

Description

Quantity of CAR-NK-CD19 CAR copies in bone marrow and peripheral blood will be determined by using quantitative polymerase chain reaction.

Time Frame

within 2 years after infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Heng Mei

Phone

027-8572600

hmei@hust.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Chenggong Li

Phone

18868112136

chenggongli@hust.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yu Hu

Organizational Affiliation

Wuhan Union Hospital, China

Official's Role

Principal Investigator

Facility Information:

Facility Name

Union Hospital, Huazhong University of Science and Technology

City

Wuhan

State/Province

Hubei

ZIP/Postal Code

430022

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Heng Mei, M.D., Ph.D

hmei@hust.edu.cn

First Name & Middle Initial & Last Name & Degree

Chenggong Li

Phone

18868112136

chenggongli@hust.edu.cn

First Name & Middle Initial & Last Name & Degree

Yu Hu, M.D., Ph.D

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32023374

Citation

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.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs