AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1NCT05445011

Anti-FLT3 CAR-T Cell (TAA05 Cell Injection) in the Treatment of Relapsed / Refractory Acute Myeloid Leukemia

A Phase 1 study testing Fludarabine + Cyclophosphamide + TAA05 Cell Injection in people with Acute Myeloid Leukemia, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a clinical trial of Anti-FLT3 CAR-T Cell (TAA05 Cell Injection) in the treatment of patients with relapsed / refractory acute myeloid leukemia. The purpose is to evaluate the safety and efficacy of anti-FLT3 CAR-T cells in patients with relapsed / refractory acute myeloid leukemia. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Fludarabine + Cyclophosphamide + TAA05 Cell Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteChina
Study dates
14 Jun 2022to 14 Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Aged 18 ~ 70 years old (including boundary value), regardless of gender;
  • FLT-3 positive acute myeloid leukemia;
  • The expected survival time was more than 3 months;
  • ECOG score 0-2;
  • Refractory or relapsed AML patients after standardized treatment who meet any of the following criteria:
  • After complete remission (CR), there were ≥5% leukemia cells or blast cells in the bone marrow(except for other reasons such as bone marrow regeneration after consolidation chemotherapy)in the peripheral blood and extramedullary lesions;
Show all 17Show fewer
  • Naive patients who are treated with 2 courses of treatment and are ineffective;
  • Those who have relapsed within 12 months after CR after consolidation and intensive treatment;
  • Those who relapse after 12 months but are ineffective after conventional chemotherapy;
  • Subjects who experienced relapses twice or multiple times; with persistent extramedullary leukemia.
  • Kidney function, cardiopulmonary function, liver function, and coagulation function meet the following requirements:
  • Creatinine ≤ 1.5 ULN;
  • Left ventricular ejection fraction ≥ 50% and echocardiography does not reveal pericardial effusions and ECG does not reveal clinically significant abnormal bands;
  • Blood oxygen saturation > 92%;
  • Total bilirubin ≤ 2 × ULN; ALT and AST ≤ 2.5 × ULN; for the patients with ALT and AST abnormalities caused by disease which researchers judge (e.g. liver infiltrates or bile duct obstruction), the indicators of which can be relaxed to ≤5× ULN;
  • PT/INR and PTT ≤ 1.5 ULN;
  • Patients understand the trial and have signed the informed consent form.

Who cannot join

  • Patients with malignant tumors other than acute myeloid leukemia within 5 years before the screening, except fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after the radical operation, and breast ductal carcinoma in situ after radical operation;
  • Patients with hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference range; Hepatitis C virus (HCV) antibody positive and hepatitis C virus (HCV) RNA positive in peripheral blood; Human immunodeficiency virus (HIV) antibody-positive; Cytomegalovirus (CMV) DNA positive; Syphilis test positive;
  • Patients with severe heart disease: including but not limited to unstable angina pectoris, myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ grade III), severe arrhythmia;
  • Patients with unstable systemic diseases judged by the researcher: including but not limited to severe liver, kidney, or metabolic diseases requiring drug treatment;
  • Within 7 days before screening, there were active or uncontrollable infections requiring systemic treatment (except mild urogenital infection and upper respiratory tract infection);
  • Pregnant or lactating women, female subjects who planned pregnancy within 2 years after cell reinfusion, or male subjects whose partners planned pregnancy within 2 years after cell reinfusion;
Show all 14Show fewer
  • Subjects who were receiving systemic steroid treatment within 7 days before screening or who were determined by the investigator to need long-term systemic steroid treatment during treatment (except inhalation or local use);
  • Participated in other clinical studies within 1 month before screening;
  • There was evidence of central nervous system invasion during subject screening(e.g. detection of tumor cells in cerebrospinal fluid or imaging suggests central infiltrates;);
  • Patients with graft-versus-host disease (GVHD) or requiring immunosuppressive agents;
  • Patients with a history of epilepsy or other central nervous system disorders;
  • Patients with primary immunodeficiency diseases;
  • Patients who are not suitable for cell construction judged by researchers;
  • Other situation researchers believe that it is not suitable for inclusion.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Heng Mei contact

027-8572600

hmei@hust.edu.cn

Chenggong Li contact

18868112136

chenggongli@hust.edu.cn

China1 site, 1 recruiting

  • Wuhan Union Hospital

    Wuhan, Hubei, 430022

    Heng Mei, M.D., Ph.D, 027-8572600, hmei@hust.edu.cn

    Zhuolin Wu, 13380211102, sherrysdreams@hotmail.com

    Recruiting

Other trials in China

About this study

Official title: Safety and Efficacy of Anti-FLT3 CAR- T Cell (TAA05 Cell Injection) in the Treatment of Relapsed/ Refractory Acute Myeloid Leukemia

This is a clinical trial of Anti-FLT3 CAR-T Cell (TAA05 Cell Injection) in the treatment of patients with relapsed / refractory acute myeloid leukemia. The purpose is to evaluate the safety and efficacy of anti-FLT3 CAR-T cells in patients with relapsed / refractory acute myeloid leukemia.

Read the detailed description

Acute myeloid leukemia (AML) is a hematological malignancy characterized by clonal proliferation of hematopoietic stem cells or progenitor cells. AML is the most common type of leukemia in adults; the 5-year survival rate is only 24%. Moreover, 40%-50% of young patients and most elderly patients eventually suffered relapses.

FMS-like tyrosine kinase 3 (FLT3) is a member of the class III receptor tyrosine kinases, mainly expressed on the cell surface of hematopoietic progenitor cells and plays an important role in normal hematopoiesis such as proliferation, differentiation and survival. The variable expression of FLT3 can be found on leukemia blasts from over 90% of AML patients. Although about 30% of AML have FLT3 gene mutations, the ectodomain of the FLT3 molecule is usually spared so that cellular immunotherapy against it has great therapeutic potential. It is shown that FLT3 expression is detected in more than half of hematopoietic stem cell (HSC) and multipotent progenitor (MPP) cells on average, while the average positive rate of lymphoid progenitor (CLP) cells is less than 20%. Since the expression level of FLT3 on hematopoietic cells is not as high as CD33 and CD123, potential hematological toxicity has been supposed to be less obstructive to the development of FLT3-CAR-T Cell products. Besides, the expression of FLT3 is not found in other normal tissues. And it is reported that FLT3 CAR T cells did not deplete CD34(+) HSCs and preserve HSC differentiation in the mice model. Therefore, conducting CAR-T cell therapy targeting the FLT3 molecule could be very promising in the clinical practice of treating AML. TAA05 Cell Injection is a kind of FLT3-targeted CAR-T cell containing an optimized CD28 costimulatory domain which could help reduce the risk of toxic side effects. This clinical trial aims to evaluate the safety and efficacy of TAA05 Cell Injection in patients with FLT3 positive AML.

Being tested
Fludarabine + Cyclophosphamide + TAA05 Cell Injection
Keywords
FLT3 positive Acute Myeloid Leukemia
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • Fludarabine + Cyclophosphamide + TAA05 Cell InjectionDrug

    Also called Fludarabine + Cyclophosphamide + Anti-FLT3 CAR-T Cell

    Fludarabine + Cyclophosphamide + TAA05 Cell Injection Fludarabine 25 mg/kg * 3d on day-7~-2; Cyclophosphamide 250 mg/kg *3d on day-7~-2; TAA05 Cell Injection on day 0.

Study groups in NCT05445011
Study groupRoleWhat they receive
TAA05 Cell InjectionExperimentalFludarabine + Cyclophosphamide + TAA05 Cell Injection Patients will receive lymphodepletion with fludarabine (25 mg/kg) and cyclophosphamide (250 mg/kg) for 3 days on day -7~-2, followed by the infusion of TAA05 Cell with the dose of 1×10^8, 2×10^8 or 4×10^8 cells on day 0. 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. After the end of dose climbing, if the maximum dose group(MTD) is still not observed, the highest dose group is defined as MTD.
Receives: Drug: Fludarabine + Cyclophosphamide + TAA05 Cell Injection

What is being measured

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

  1. Maximal tolerable dose (MTD)

    Fludarabine + Cyclophosphamide + TAA05 Cell Injection Patients will receive lymphodepletion with fludarabine (25 mg/kg) and cyclophosphamide (250 mg/kg) for 3 days on day -7~-2, followed by the infusion of TAA05 Cell with the dose of 1×10^8, 2×10^8 or 4×10^8 cells on day 0. 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. MTD is defined as the highest dose at which DLT occurs in no more than 2 of the 6 patients. After the end of dose climbing, if the maximum dose group(MTD) is still not observed, the highest dose group is defined as MTD.

    Measured: within 2 yeas after infusion

Secondary outcomes (7)

  1. Incidence of Treatment-related Adverse Events

    Adverse events will be assessed according to NCI-CTCAE v5.0, cytokine release syndrome and CAR-T cell-related encephalopathy syndrome will be assessed according to ASTCT criteria.

    Measured: within 2 yeas after infusion

  2. Overall response rate(ORR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

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

    Measured: within 2 yeas after infusion

  3. Complete response rate(CRR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

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

    Measured: within 2 yeas after infusion

  4. Overall survival(OS) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

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

    Measured: within 2 yeas after infusion

  5. Progress-free survival(PFS) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

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

    Measured: within 2 yeas after infusion

  6. Duration of Response(DOR) of administering Anti-FLT3 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

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

    Measured: within 2 yeas after infusion

  7. In vivo expansion and survival of Anti-FLT3 CAR-T Cell

    Quantity of CAR copies in bone marrow and peripheral blood will be determined by using qPCR.

    Measured: within 2 yeas 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 posted6 Jul 2022
  2. Study start14 Jun 2022
  3. Primary completion14 Jun 2025 (estimated)
  4. Study completion14 Jun 2027 (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
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05445011
Sponsor's protocol ID
Anti-FLT3 CAR-T Cell
Status last verified
Jun 2022
First submitted
23 Jun 2022
Last updated
6 Jul 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chen L, Mao H, Zhang J, Chu J, Devine S, Caligiuri MA, Yu J. Targeting FLT3 by chimeric antigen receptor T cells for the treatment of acute myeloid leukemia. Leukemia. 2017 Aug;31(8):1830-1834. doi: 10.1038/leu.2017.147. Epub 2017 May 12. No abstract available.

    PubMed 28496177

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fludarabine + Cyclophosphamide + TAA05 Cell Injection in people with 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 17 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: looking for participants now, as of the sponsor's last update on 6 Jul 2022. 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?

This study is still under way. Results are not available in the source record yet.

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?

Maximal tolerable dose (MTD) (time frame: within 2 yeas 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 NCT05445011, 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 6 Jul 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in