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NHL, AdultPhase 1NCT05758610

A Phase I Study of Euthare-155008(ETH-155008) in AML and NHL Patients

A Phase 1 study testing ETH-155008 in people with NHL, Adult and AML, Adult Recurrent, run by Shengke Pharmaceuticals (Jiangsu) Limited, China 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 The sponsor has not verified this record for over two years, so it may be out of date.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 Trial is an open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ETH-155008 in subjects with AML and NHL who previously received standard treatment or are ineligible for standard treatment options. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NHL, Adult, AML, Adult Recurrent
What is being tested?
ETH-155008
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
2 sitesChina
Study dates
4 Nov 2022to Jun 2026
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

  • Be at least 18 years of age and < 80 years old.
  • Must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the trial and are willing to participate in the trial prior to any other trial-related assessments or procedures, and can communicated with investigators and are willing to comply with the protocol.
  • Has histologically or cytologically confirmed relapsed and/or refractory acute myelocytic leukemia(AML) or non-Hodgkin's lymphoma(NHL) with no available standard therapy or is not a candidate for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with ETH-155008 may be beneficial. In addition, the following disease-specific criteria outlined below must be met.
  • For all indolent NHL (Follicular Lymphoma[FL], Marginal Zone Lymphoma[MZL] and Waldenström Macroglobulinemia[WM]), previously treated with at least 2 prior lines of systemic therapy with at least 1 line being an anti-cluster of differentiation antigen 20(anti-CD20) antibody-containing combination regimen. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), prior treatment with at least 2 lines of systemic therapy, including Bruton's tyrosine kinase(BTK) inhibitors or B-cell lymphoma-2(BCL-2) inhibitors, is required.
  • For mantle cell lymphoma(MCL), prior treatment with at least 2 lines of systemic therapy (including a combination regimen of anti-CD20 antibodies and BTK inhibitors) and no other approved therapy considered more appropriate by the investigators.
  • For aggressive B-NHL (diffuse large B cell lymphoma[DLBCL], highly malignant B-cell lymphoma[HGBCL], and primary mediastinal large B-cell lymphoma[PMBCL]), patients who can tolerate intensive therapy or autologous hematopoietic stem cell transplantation are required to have received standard second-line therapy in the past but have failed or relapsed. If patients cannot tolerate intensive therapy or autologous hematopoietic stem cell transplantation, they must have received standard first-line therapy in the past, but therapy failed or relapsed.
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  • For T-NHL, it is required to have been adequately treated with a systemic standard dose of drugs in the past without remission or recurrence.
  • For AML, relapsed/refractory AML diagnosed according to the World Health Organization (WHO) classification in 2016, for which no standard treatment is available or for which standard treatment is not tolerated; According to Chinese Guidelines for the Diagnosis and Treatment of Relapsed and Refractory acute myeloid Leukemia (2021 Edition), the definition of relapsed and refractory is as follows:
  • <!-- -->
  • Recurrent AML: recurrence of leukemia cells in peripheral blood or original cells in bone marrow ≥ 5% after CR (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration.
  • Refractory AML: initial patients who failed to respond to 2 courses of treatment with standard protocols; Patients with CR relapse within 12 months after consolidation and intensive treatment; Patients who relapse after 12 months but fail to respond to conventional chemotherapy; Patients with two or more relapses; Extramedullary leukemia persists.
  • For NHL, measurable lesions that meet the efficacy evaluation criteria for Lugano lymphoma (Cheson 2014) are required(at least one intranodular lesion longest diameter (LDi)﹥1.5 cm, or at least 1 extranodal lesion LDi﹥1 cm). For WM patients, immunoglobulin M(IgM) should be greater than 5g/L. For chronic lymphocytic leukemia(CLL) patients, monoclonal B lymphocytes greater than 5×109/L are required. For patients with AML, bone marrow primordial cells at baseline are required to be at least 5%.
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 (dose escalation cohorts) or ≤2 (dose expansion cohorts).
  • For NHL, hematology laboratory parameters must be within the following ranges. Values must be without transfusions or growth factors for at least 7 days prior to the first dose of study drug ,
  • Hemoglobin (HB) ≥80g/L; In case of bone marrow invasion, hemoglobin ≥60g/L is required (red blood cell infusion is allowed prior to initial administration).
  • Platelet (PLT) count ≥75×10^9/L; In case of bone marrow invasion, platelet count ≥50×10^9/L (50,000/μL) is required.
  • Absolute count of neutrophil granulocyte (ANC) ≥1.0×10^9/L; Absolute neutrophil count ≥0.75×10^9/L (750/μL) is required if bone marrow invasion is present.
  • For AML, there is no upper limit on white blood cell count (WBC) at screening, but it is required before the first administration of the investigational drug WBC﹤25×10^9/L. Note: Subjects with excess primitive cells may be treated with hydroxyurea until 2 days prior to initial administration of the study drug to reduce WBC.
  • Blood biochemical test results must be within the following range:
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5×upper limit of normal (ULN). If the subject has primary liver invasion, ALT, AST ≤5×ULN is required.
  • Total bilirubin(TBIL) ≤1.5×ULN. If the subject has primary liver invasion, TBIL ≤3×ULN is required.
  • Creatinine clearance rate(CCr)≥45 ml/min (Cockcroft-Gault formula).
  • Prothrombin time(PT) and activated partial thromboplastin time(aPTT) ≤1.5×ULN.
  • Life expectancy of at least 3 months.
  • A woman of childbearing potential must have a negative serum beta-human chorionic gonadotropin (beta-hCG) at screening and prior to the first dose of study drug.
  • Women must be: a. Not of childbearing potential b. Of childbearing potential and - Practicing a highly effective, preferably user-independent method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study drug and until 90 days after last dose.
  • In addition to the user-independent, highly effective method of contraception, a male or female condom is required. Male condoms and female condoms should not be used together (due to risk of failure with friction).
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with or partner with occlusive cap (diaphragm or cervical/vault caps).
  • Men or women must agree not to donate sperm or eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after the last study drug administration.
  • Must be willing and able to adhere to the requirements and restrictions specified in the ICF and this protocol.

Who cannot join

  • Acute promyelocytic leukemia, acute mixed phenotypic leukemia, acute myeloid leukemia with Philadelphia chromosome (Ph chromosome) positive.
  • AML with myeloid sarcoma.
  • The central nervous system (CNS) is known to be involved.
  • Previous solid organ transplantation.
  • Previously received allogeneic hematopoietic stem cell transplantation.
  • The patient received autologous hematopoietic stem cell transplantation (HSCT) within 3 months prior to initial administration of ETH-155008.
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  • Have an active autoimmune disease within the past 2 years that requires treatment with systemic immunosuppressive drugs (i.e., long-term corticosteroids, methotrexate, or tacrolimus).
  • Toxicities from previous anti-cancer therapies have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
  • Has known past or current malignancy other than inclusion diagnosis, except for:
  • Cervical carcinoma of Stage ⅠB or less.
  • Non-invasive basal cell or squamous cell skin carcinomas.
  • Non-invasive, superficial bladder cancer.
  • Prostate cancer with a current prostate-specific antigen(PSA) level < 0.1 ng/mL.
  • malignancy which in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 1 year before the first dose of study drug.
  • Any curable cancer with a complete response(CR) of > 2 years duration.
  • Prior treatment with a cyclin dependent kinase 4 and 6(CDK4/6) or Pim inhibitor.
  • Known allergies, hypersensitivity, or intolerance to ETH-155008 or its excipients.
  • Prior chemotherapy or targeted therapy within 2 weeks(Or five half-lives, which is the longer) prior to first dosing treatment, or treatment with an investigational anticancer agent or radiotherapy (including investigational vaccines) within 4 weeks before the first administration of ETH-155008. For investigational agents where half-life is known, there should be a treatment-free window of at least 2 weeks or 5 half-lives.
  • Prior chimeric antigen receptor T-Cell(CAR-T) immunotherapy within 12 weeks before the first administration of ETH-155008.
  • Corticosteroids >10 mg daily prednisone equivalents:
  • A short course (ie, >10 mg daily prednisone equivalents for less than 7 days) of corticosteroids is permitted. Inhaled or topical steroids, and adrenal replacement doses ≤10 mg daily prednisone equivalents, are permitted in the absence of active autoimmune disease.
  • History of clinically significant cardiovascular disease within the 6 months prior to the first dose of study drug including, but not limited to:
  • Corrected QT interval (QT interval corrected using Fridericia formula [QTcF]) female﹥470ms, male﹥450ms.
  • Myocardial infarction
  • Severe or unstable angina
  • Clinically significant cardiac arrhythmias
  • Uncontrolled (persistent) hypertension: systolic blood pressure >159 mmHg; diastolic blood pressure >99 mmHg
  • Stroke or transient ischemic attack
  • Venous thromboembolic events (i.e., pulmonary embolism) within 1 month prior to the first dose of study drug
  • Congestive heart failure (New York Heart Association class III-IV)
  • Pericarditis or clinically significant pericardial effusion
  • Myocarditis
  • Endocarditis
  • Clinically significant pulmonary compromise, particularly the need for supplemental oxygen to maintain adequate oxygenation.
  • Unable to swallow capsules or tablets or malabsorption syndrome, disease significantly affecting GI function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction. If any of these conditions exist, the site should discuss with the sponsor to determine subject eligibility.
  • Evidence of active viral, bacterial, or uncontrolled systemic fungal infection requiring parenteral treatment within 2 weeks before the first dose of study drug.
  • Active or chronic hepatitis B or hepatitis C infection.
  • Hepatitis B infection is defined by a positive test for hepatitis B surface antigen (HBsAg)
  • Or HBsAg negative and positive for anti-hepatitis B core antigen (HBc) with hepatitis B virus(HBV) DNA﹥ULN
  • Hepatitis C infection is defined by a positive hepatitis C virus (HCV) ribonucleic acid (RNA).
  • Tested HIV positive at screening.
  • Syphilitic antibody positive.
  • Trauma or major surgery (e.g., requiring general anesthesia) within 28 days prior to the first dose of study drug. Note: Subjects with planned surgical procedures to be conducted under local anesthesia may participate.
  • Any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse), dementia or altered mental status; or any issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent, or that in the opinion of the investigator would contraindicate the participation in the study or confound the protocol-specified assessments or results of the study.
  • Requires a prohibited medication that cannot be discontinued or substituted, or temporally interrupted during the study.
  • A drug used as a substrate for cytochrome P450 3A4(CYP3A4) within 1 week (or 5 half-lives, whichever was longer) prior to initial treatment.
  • Overactive CYP3A4 or P-glycoprotein inducers or inhibitors were used within 1 week (or 5 half-lives, if older) prior to initial treatment.
  • A woman who is pregnant or breastfeeding.
  • Other patients judged by the investigator to be unsuitable for inclusion.

Trial locations and contacts

2 sites in 1 country.

James Zhang, Master contact

+86 512 68098859

james_zhang@shengketx.com

China2 sites, 2 recruiting

  • Hematology Hospital, Chinese Academy of Medical Sciences

    Tianjin, Tianjin Municipality, 300020

    May Zuo, may_zuo@shengketx.com

    Jianxiang Wang, Doctor

    Recruiting

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450003

    May Zuo, may_zuo@shengketx.com

    Keshu Zhou, Doctor

    Not yet recruiting

Other trials in China

About this study

Official title: A Phase I Clinical Study of Safety, Tolerability, Pharmacokinetics, and Initial Efficacy of ETH-155008 Tablets in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Non-Hodgkin's Lymphoma

This Trial is an open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ETH-155008 in subjects with AML and NHL who previously received standard treatment or are ineligible for standard treatment options.

Read the detailed description

The primary objectives of this study are to evaluate the safety of ETH-155008 and to determine the recommended Phase 2 dose (RP2D) regimen or the maximum tolerated dose (MTD). Secondary objectives and endpoints will evaluate the pharmacokinetics(PK) and pharmacodynamics(PD) of ETH-155008 and preliminary clinical anti-tumor activity of ETH-155008 in subjects with R/R acute myeloid leukemia (AML) and Non-Hodgkin's lymphoma (NHL).

This Trial is an open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ETH-155008 in subjects with R/R AML and NHL who previously received standard treatment or are ineligible for standard treatment options. The study will be conducted in 2 parts: dose escalation (Part 1) and cohort expansion (Part 2). In the dose escalation, ETH-155008 will be administrated orally, once daily (QD) for 28 days at 5 dose levels ranging from 20 mg to 100 mg in 28-day cycles. Dose-limiting toxicity (DLT) will be assessed during the first treatment cycle and the maximum tolerated dose (MTD) will be identified. Additional subjects will be treated in the dose expansion at the commended phase 2 dose (RP2D).

During the study, safety will be monitored by the data review committee (DRC) at each dose escalation step and at regular intervals during cohort expansion. Continuous reassessment for DLTs will help minimize the potential risks associated with the study drug. Cumulative data from subsequent treatment cycles will also be monitored for late-onset toxicities.

Being tested
ETH-155008
Medical subject headings
Lymphoma, Non-Hodgkin, Leukemia, Myeloid, Acute, Recurrence

What participants receive

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

  • ETH-155008Drug

    Also called Study drug

    ETH-155008 is an orally bioavailable, potent Pim-3 and CDK4/6 dual kinase inhibitor.

    Dosage form: 10mg, 20 mg and 40 mg, tablets. ETH-155008 tablets should be taken while fasting, either 1 hour before or 2 hours after a meal.

Study groups in NCT05758610
Study groupRoleWhat they receive
ETH-155008ExperimentalDose level: 20mg/day, 40mg/day, 60mg/day, 80mg/day, 100mg/day. Each dose level will recruit 1-6 subjects, taking ETH-155008 tablets once daily. Intervention: Drug: ETH-155008
Receives: Drug: ETH-155008

What is being measured

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

  1. Incidence and severity of adverse events

    Determine the safety of ETH-155008 in subjects with R/R AML and NHL

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  2. Dose Limiting Toxicity (DLTs)

    Incidence of DLTs in the first treatment cycle of ETH-155008

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  3. The RP2D(s) or the MTD of ETH-155008 in subjects with R/R AML and NHL

    The RP2D is the maximum tolerated dose (MTD) or less.

    Measured: At the end of Cycle 1 (each cycle is 28 days)

Secondary outcomes (12)

  1. PK parameter of ETH-155008: Cmax

    Maximum Concentration (Cmax) of ETH-155008

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  2. PK parameter of ETH-155008: Tmax

    Time of First Occurrence of Cmax for ETH-155008

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  3. PK parameter of ETH-155008: AUC

    area under the curve (AUC)

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  4. Disease evaluation of efficacy of ETH-155008: ORR

    objective response rate(ORR)

    Measured: 12 months post first dosing

  5. Disease evaluation of efficacy of ETH-155008: CR

    complete response(CR)

    Measured: 12 months post first dosing

  6. Disease evaluation of efficacy of ETH-155008: PR

    partial response(PR)

    Measured: 12 months post first dosing

  7. Disease evaluation of efficacy of ETH-155008: DCR

    disease control rate(DCR)

    Measured: 12 months post first dosing

  8. Disease evaluation of efficacy of ETH-155008: TTR

    time to response(TTR)

    Measured: 12 months post first dosing

  9. Disease evaluation of efficacy of ETH-155008: DOR

    duration of response(DOR)

    Measured: 12 months post first dosing

  10. Assess the PD of ETH-155008: Inhibition of Pim kinase

    Inhibition of Pim kinases

    Measured: 2 months post first dosing

  11. Assess the PD of ETH-155008: Inhibition of CDK4/6 kinase

    Inhibition of cyclin-dependent kinase 4 and 6(CDK4/6)

    Measured: 2 months post first dosing

  12. Assess the PD of ETH-155008: Inhibition of FLT3 kinase

    Inhibition of Feline McDonough sarcoma-like tyrosine kinase 3(FLT3)

    Measured: 2 months post first dosing

Timeline

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

  1. First posted7 Mar 2023
  2. Study start4 Nov 2022
  3. Primary completionDec 2025 (estimated)
  4. Study completionJun 2026 (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
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05758610
Sponsor's protocol ID
ETH-155008- 101
Status last verified
May 2024
First submitted
15 Feb 2023
Last updated
8 May 2024
Results posted
No
Data monitoring committee
Yes
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 ETH-155008 in people with NHL, Adult and AML, Adult Recurrent, run by Shengke Pharmaceuticals (Jiangsu) Limited, China 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 30 inclusion and 49 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 May 2024. 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 James Zhang, Master (+86 512 68098859, james_zhang@shengketx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (time frame: At the end of Cycle 1 (each cycle is 28 days)). The study lists 3 primary outcomes in all. 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 NCT05758610.

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 May 2024.

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