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CD123+ Acute Myeloid LeukemiaPhase 1NCT04014881

Safety and Efficacy of Anti-CD123 CAR-T Therapy in Patients With Refractory/ Relapsed CD123+ Acute Myeloid Leukemia.

A Phase 1 study testing Third-generation anti-CD123 CAR-T cells in people with CD123+ Acute Myeloid 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 The sponsor has not verified this record for over two years, so it may be out of date.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 safety and efficacy of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
CD123+ Acute Myeloid Leukemia
What is being tested?
Third-generation anti-CD123 CAR-T cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteChina
Study dates
6 Jul 2019to 1 Jul 2022
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathological and histological examination confirmed CD123+ refractory or relapsed Acute Myeloid Leukemia.
  • Diagnostic criteria for recurrent AML: After complete remission (CR), leukemia cells or bone marrow primordial cells > 0.050 (except for bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration appears again in peripheral blood.
  • B.Diagnostic criteria for refractory AML(Meeting one of the following)
  • ineffectiveness after the first standard regimen treatment of 2 courses.
  • patients relapse within 12 months after consolidation and intensive treatment after CR.
  • Patients relapse 12 months later and fail to respond to conventional chemotherapy.
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  • Patients with two or more recurrences.
  • Patients with persistent extramedullary leukemia.
  • Patients with recurrence after CR and unsuitable for HSCT (auto/allo-HSCT).
  • Aged 18 to 70 years (including 18 and 70 years old).
  • At least one measurable or evaluable lesion:AML patients with positive or relapsed positive bone marrow MRD.
  • ECOG≤ 2 and expected lifetime ≥3 months.
  • Adequate organ function:
  • Liver function: ALT/AST≤3 ULN. Total bilirubin≤2 ULN.
  • Renal function: eGFR> 60 mL/min/1.73 m2, or creatinine clearance ≥45mL/min.
  • Lung function: Carbon Monoxide (DLCO) or Forced Expiratory Volume in the first second (FEV1) > 45% predicted.
  • Cardiac function: LVEF ≥ 50%.
  • The patients did not receive any anticancer treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before admission, and the toxicity related to previous treatments had returned to < 1 level at admission (except for low toxicity such as alopecia).
  • Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.
  • Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Who cannot join

  • Women who are pregnant (urine/blood pregnancy test positive) or lactating.
  • Male or female with a conception plan in the past 1 years.
  • Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment.
  • Uncontrolled infectious disease within 4 weeks prior to enrollment.
  • Active hepatitis B/C virus.
  • HIV infected patients.
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  • Suffering from a serious autoimmune disease or immunodeficiency disease.
  • The patient is allergic and is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
  • The patient participated in other clinical trials within 6 weeks prior to enrollment.
  • Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
  • Suffering from mental illness.
  • Patient has drug abuse/addiction.
  • Central nervous system involvement.
  • According to the investigator's judgment, the patient has other unsuitable grouping conditions.

Trial locations and contacts

1 site in 1 country.

Yu Hu, M.D., Ph.D contact

86-13986183871

dr_huyu@126.com

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

86-13886160811

hmei@hust.edu.cn

China1 site, 1 recruiting
  • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

    Wuhan, Hubei, 430022

    Yu Hu, M.D., Ph.D, 86-13986183871, dr_huyu@126.com

    Heng Mei, M.D., Ph.D, 86-13886160811, hmei@hust.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Single-center, Open-label, Single-arm Clinical Study of Efficacy and Safety of Anti-CD123 CAR-T Therapy in Patients With Refractory/Relapsed CD123+ Acute Myeloid Leukemia.

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia.

Read the detailed description

CD123 is a transmembrane subunit of the IL-3 receptor expressed on AML blasts. The investigators have conducted a third generationCD123-targeted CAR containing CD137 and CD28 costimulatory domains.This study aims to evaluate the safety and efficacy of anti-CD123 CAR-T cells in patients with relapsed/refractory CD123+ Acute Myeloid Leukemia.

Being tested
Third-generation anti-CD123 CAR-T cells

What participants receive

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

  • Third-generation anti-CD123 CAR-T cellsBiological

    From the minimum dose, 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.

Study groups in NCT04014881
Study groupRoleWhat they receive
CD123+ Acute Myeloid LeukemiaExperimentalPatients will receive CD123-targeted CAR-T cells in the dose-climbing trial. Each dose group has 3 patients and the the maximum dose can be extended.
Receives: Biological: Third-generation anti-CD123 CAR-T 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 4.0).

    Measured: 3 years

Secondary outcomes (6)
  1. Overall remission rate(ORR) of anti-CD123 CAR-T Therapy in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

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

    Measured: 3 years

  2. Overall survival(OS) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

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

    Measured: 3 years

  3. Duration of Response(DOR) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

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

    Measured: 3 years

  4. Progress-free survival(PFS) of anti-CD123 CAR-T cells in patients with refractory/relapsed CD123+ Acute Myeloid Leukemia

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

    Measured: 3 years

  5. Rate of anti-CD123 CAR-T cells in bone marrow cells and peripheral blood cells

    In vivo (bone marrow and peripheral blood) rate and quantity of anti-CD123 CAR-T cells were determined by means of flow cytometry.

    Measured: 3 years

  6. Quantity of anti-CD123 CAR copies in bone marrow cells and peripheral blood cells

    In vivo (bone marrow and peripheral blood) quantity of anti-CD123 CAR copies were determined by means of qPCR.

    Measured: 3 years

Timeline

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

  1. First posted10 Jul 2019
  2. Study start6 Jul 2019
  3. Primary completion1 Jul 2021 (estimated)
  4. Study completion1 Jul 2022 (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
Model description
This study was a single-center, open-label, single-arm, non-randomized,3+3 dose escalation clinical trial.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.
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04014881
Sponsor's protocol ID
WHUH-CART-CD123-01
Status last verified
Aug 2019
First submitted
2 Jul 2019
Last updated
7 Aug 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Hansrivijit P, Gale RP, Barrett J, Ciurea SO. Cellular therapy for acute myeloid Leukemia - Current status and future prospects. Blood Rev. 2019 Sep;37:100578. doi: 10.1016/j.blre.2019.05.002. Epub 2019 May 11.

    PubMed 31109711
  • Arcangeli S, Rotiroti MC, Bardelli M, Simonelli L, Magnani CF, Biondi A, Biagi E, Tettamanti S, Varani L. Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia. Mol Ther. 2017 Aug 2;25(8):1933-1945. doi: 10.1016/j.ymthe.2017.04.017. Epub 2017 May 4.

    PubMed 28479045
  • Cartellieri M, Feldmann A, Koristka S, Arndt C, Loff S, Ehninger A, von Bonin M, Bejestani EP, Ehninger G, Bachmann MP. Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts. Blood Cancer J. 2016 Aug 12;6(8):e458. doi: 10.1038/bcj.2016.61.

    PubMed 27518241
  • Tettamanti S, Biondi A, Biagi E, Bonnet D. CD123 AML targeting by chimeric antigen receptors: A novel magic bullet for AML therapeutics? Oncoimmunology. 2014 May 14;3:e28835. doi: 10.4161/onci.28835. eCollection 2014.

    PubMed 25083319
  • Tasian SK, Kenderian SS, Shen F, Ruella M, Shestova O, Kozlowski M, Li Y, Schrank-Hacker A, Morrissette JJD, Carroll M, June CH, Grupp SA, Gill S. Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia. Blood. 2017 Apr 27;129(17):2395-2407. doi: 10.1182/blood-2016-08-736041. Epub 2017 Feb 28.

    PubMed 28246194
  • Mardiros A, Dos Santos C, McDonald T, Brown CE, Wang X, Budde LE, Hoffman L, Aguilar B, Chang WC, Bretzlaff W, Chang B, Jonnalagadda M, Starr R, Ostberg JR, Jensen MC, Bhatia R, Forman SJ. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood. 2013 Oct 31;122(18):3138-48. doi: 10.1182/blood-2012-12-474056. Epub 2013 Sep 12.

    PubMed 24030378

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Third-generation anti-CD123 CAR-T cells in people with CD123+ Acute Myeloid 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 20 inclusion and 14 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 7 Aug 2019. 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 Yu Hu, M.D., Ph.D (86-13986183871, dr_huyu@126.com), 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: 3 years). 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 NCT04014881, which also lists 6 linked publications.

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 7 Aug 2019.

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