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AzTrials

Acute Lymphocytic LeukemiaPhase 1NCT04796675

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

A Phase 1 study testing Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells in people with Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteChina
Study dates
10 Apr 2021to 10 Mar 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Heng Mei contact

027-8572600

hmei@hust.edu.cn

Chenggong Li contact

18868112136

chenggongli@hust.edu.cn

China1 site, 1 recruiting

  • Union Hospital, Huazhong University of Science and Technology

    Wuhan, Hubei, 430022

    Heng Mei, M.D., Ph.D, hmei@hust.edu.cn

    Chenggong Li, 18868112136, chenggongli@hust.edu.cn

    Recruiting

Other trials in China

About this study

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

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.

Read the 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.

Being tested
Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fludarabine + Cyclophosphamide + CAR-NK-CD19 CellsDrug

    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.

Study groups in NCT04796675
Study groupRoleWhat they receive
Fludarabine + Cyclophosphamide + CAR-NK-CD19 CellsExperimentalPatients 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.
Receives: Drug: Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: within 2 years after infusion

Secondary outcomes (5)

  1. 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).

    Measured: within 2 years after infusion

  2. 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).

    Measured: within 2 years after infusion

  3. 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).

    Measured: within 2 years after infusion

  4. 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).

    Measured: within 2 years after infusion

  5. 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).

    Measured: within 2 years after infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2021
  2. Study start10 Apr 2021 (estimated)
  3. Primary completion10 Mar 2023 (estimated)
  4. Study completion10 Mar 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04796675
Sponsor's protocol ID
CAR-NK-CD19 cells
Status last verified
Apr 2021
First submitted
10 Mar 2021
Last updated
8 Apr 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32023374

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells in people with Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Heng Mei (027-8572600, hmei@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-related Adverse Events (time frame: within 2 years after infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04796675, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.

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