Clinical trial NCT04796675: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Lymphocytic Leukemia
Chronic Lymphocytic Leukemia
Non Hodgkin's Lymphoma
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: Shanghai Simnova Biotechnology Co.,Ltd.
First posted: 2021-03-15
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Aged ≥ 18 years;
2. Eastern Cooperative Oncology Group score≤ 3;
3. Diagnosed as CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia and Non Hodgkin's lymphoma.
4. Patients must relapse or be refractory after at least two lines of therapy.
5. 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.
6. Negativity of blood pregnancy test for woman, and participants use effective methods of contraception until last follow-up.
7. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

Exclusion Criteria:

1. 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.
2. Patients with graft-versus-host reaction and need immunosuppressive agents, or patients with autoimmune diseases.
3. Systemic steroids are used within 5 days before apheresis.
4. Drugs to stimulate the production of bone marrow hematopoietic cells are used within 5 days before apheresis.
5. 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).
6. History of epilepsy or other central nervous system diseases.
7. Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within five years.
8. Known HIV positive patients.
9. Patients with active infections, including active replication of hepatitis B or active hepatitis C.
10. 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).
11. Major surgery in the past 4 weeks.
12. Non-compliant patients.
13. Anticoagulants are being used.

Primary outcomes:
measure: Incidence of Treatment-related Adverse Events
timeFrame: within 2 years after infusion
Secondary outcomes:
measure: Overall response rate(ORR) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
timeFrame: within 2 years after infusion
measure: Complete response rate(CRR) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
timeFrame: within 2 years after infusion
measure: Progress-free survival(PFS) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
timeFrame: within 2 years after infusion
measure: Duration of Response(DOR) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
timeFrame: within 2 years after infusion
measure: Overall survival(OS) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
timeFrame: within 2 years after infusion
Other outcomes:
measure: In vivo expansion and survival of CAR-NK-CD19 cells
timeFrame: within 2 years after infusion
Locations:
city: Wuhan
country: China
facility: Union Hospital, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Yu Hu
role: PRINCIPAL_INVESTIGATOR
References:
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.