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Acute Lymphoblastic LeukemiaPhase 1NCT04796688

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

A Phase 1 study testing Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells in people with Acute Lymphoblastic Leukemia and Chronic Lymphoblastic Leukemia, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 2 sites 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 The sponsor has not verified this record for over two years, so it may be out of date.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 universal chimeric antigen receptor-modified AT19 cells in patients with relapsed or refractory hematological malignancies. Read more about this study

Who is it for?
Ages 14 to 78 years
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
2 sitesChina
Study dates
10 Mar 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 14 to 78 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
  • Refractory/relapsed B-cell lymphoblastic leukemia, meeting one of the following criteria:
  • Recurrence within 6 months after first remission. ii. Primary refractory disease which cannot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.
  • Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.
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  • Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.
  • 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.
  • 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.
  • 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:
  • Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.
  • 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:
  • Liver function: ALT/AST < 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.
  • Estimated survival time≥3 months.
  • Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

Heng Mei, M.D., Ph.D contact

027-8572600

hmei@hust.edu.cn

Chenggong Li contact

18868112136

chenggongli@hust.edu.cn

China2 sites, 2 recruiting

  • Union Hospital, Huazhong University of Science and Technology

    Wuhan, Hubei, 430022

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

    Chenggong Li, chenggongli@hust.edu.cn

    Recruiting

  • Union Hospital, Huazhong University of Science and Technology

    Wuhan, Hubei, 430022

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

    Chenggong Li, chenggongli@hust.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Safety and Efficacy of Universal Chimeric Antigen Receptor-modified AT19 Cells in Patients With CD19+ Relapsed/Refractory Hematological 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 universal chimeric antigen receptor-modified AT19 cells in patients with relapsed or refractory hematological malignancies.

Read the detailed description
  • Adoptive transfer of autologous anti-CD19 CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies, including CD19+ B-cell acute lymphoblastic leukemia(B-ALL), B-cell chronic lymphoblastic leukemia(B-CLL), and B-cell lymphoma.
  • However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and variable clinical activity.
  • Healthy donor T cells can provide a source for production of universal CAR-T cells when combined with gene editing to prevent expression of endogenous TCRs and avoid generation of GvHD in HLA mismatched recipients.
  • Cord blood derived T cells from healthy donor are the source for production of universal anti-CD19 CAR-modified AT19 cells. CRISPR/cas9 gene-editing technology has been used to knockout TCRs and HLA-I to avoid GvHD and transplant rejection.
  • AT19 cells have exhibited potent cytotoxicity in CD19+ tumor cells and can effectively eradicate CD19+ tumor cells in xenograft mice models, without showing GvHD.
  • This study aims to evaluate prelimary safety and efficacy of the universal AT19 cells in patients with relapsed/refractory B-ALL, B-CLL, and B-cell lymphoma.
Being tested
Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell

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 NCT04796688
Study groupRoleWhat they receive
Fludarabine + Cyclophosphamide + AT19 cellsExperimentalPatients 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.
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 AT19 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 AT19 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 AT19 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: 2 years after infusion

  4. Duration of Response(DOR) of administering AT19 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: 2 years after infusion

  5. Overall survival(OS) of administering AT19 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: 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 Mar 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
NCT04796688
Sponsor's protocol ID
Universal AT19 cells
Status last verified
Mar 2021
First submitted
10 Mar 2021
Last updated
15 Mar 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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 Lymphoblastic Leukemia and Chronic Lymphoblastic Leukemia, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 2 sites 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 18 inclusion and 11 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 15 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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, M.D., Ph.D (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 NCT04796688.

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 15 Mar 2021.

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