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NHLPhase 1NCT04840784

First-in Human (FIH) Trial of ETH-155008 in Subjects With B-NHL, CLL/SLL and AML

A Phase 1 study testing ETH-155008 in people with NHL and Leukemia, run by Shengke Pharmaceuticals Pty Ltd at 5 sites in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This Trial is a FIH, open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ETH-155008 in subjects with R/R B-cell NHL, CLL/SLL and AML who previously received standard treatment or are ineligible for standard treatment options. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
NHL, Leukemia
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
9 participants
Where
5 sitesAustralia
Study dates
29 Jun 2021to 2 May 2023
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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each potential subject must fulfil all of the following criteria to be enrolled in the study.
  • 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. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard of care for the subject's disease.
  • Has histologically or cytologically confirmed relapsed and/or refractory B-cell NHL, CLL/SLL or AML 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 (FL, MZL and Waldenström Macroglobulinemia), previously treated with at least 2 prior lines of systemic therapy with at least 1 line being an anti-CD20 antibody-containing combination regimen.
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  • For aggressive NHL (DLBCL, HGBCL, and PMBCL), received, or not eligible for high-dose chemotherapy containing anti-CD20 monoclonal antibodies and autologous stem cell transplantation with curative intent.
  • For MCL, previously treated with at least 1 prior line of systemic therapy including an anti-CD20 antibody combination regimen, with no other approved therapies that would be more appropriate in the investigator's judgement.
  • For CLL/SLL, relapsed or refractory with at least 2 prior lines of systemic therapy using different treatment regimens including BTK inhibitors or venetoclax.
  • For AML, AML diagnosis according to the 2016 World Health Organization (WHO) classification who have received no more than 3 prior lines of therapy and with no available therapy.
  • Has one of the following RB POSITIVE B-cell NHL subtypes or AML for the Dose Expansion:
  • Aggressive NHL (DLCBL, HGBCL and PMBCL)
  • MCL,
  • AML Note: at screening, archived or fresh tumor tissue will be assayed by local sites and may need to be confirmed by a central lab later to evaluate Rb expression. Rb IHC staining intensity will be deemed positive if a staining level of 1+ or greater above background is identified.
  • Presence of measurable or evaluable disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 (dose escalation cohorts) or ≤2 (dose expansion cohorts) (Appendix 1).
  • For B-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 ≥8 g/dL
  • Platelets ≥75×109 /L
  • Absolute neutrophil count ≥1.0×109 /L
  • If neutropenia or thrombocytopenia is believed to be due to marrow infiltration with malignant cells then the absolute neutrophil 0.75x10 9 /L (750/µL) or platelet count ≥ 50x10 9 /L (50,000/µL).
  • For AML, WBC count, no upper limit at Screening, but must be <10 x109/L on Day 1 prior to the first dose of study drug. Note: Subjects with excessive blasts may be treated with hydroxyurea until 2 days prior to first dose of study drug to reduce WBC; Platelet count >10,000/µL; Platelet transfusion prior to first dose is permitted.
  • INR/PT and aPTT ≤1.5 times institutional upper limit of normal (ULN).
  • Clinical chemistry laboratory parameters must be within the following range:
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), GGT, and alkaline phosphatase ≤2.5×upper limit of normal (ULN).
  • Serum total bilirubin ≤1.5×the ULN.
  • Creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
  • Cardiac parameters within the following range: corrected QT interval (QTc intervals corrected using Fridericia's formula [QTcF]) ≤470 milliseconds based on the average of triplicate assessments performed no more than 5 minutes apart (±3 minutes).
  • 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 (as defined in Appendix 3, Contraceptive Guidance and Pregnancy): 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. Examples of highly effective methods of contraception are in Appendix 3, Contraceptive Guidance and Pregnancy.
  • 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.
  • For Part 2 (dose expansion): for B-cell NHL, tumor tissue availability is required at baseline unless clinically contraindicated.
  • Must be willing and able to adhere to the requirements and restrictions specified in the ICF and this protocol.

Who cannot join

  • Any potential subject who meets any of the following criteria will be excluded from participating in the trial.
  • Primary central nervous system (CNS) lymphoma or known CNS involvement at screening, unless treated and stable for ≥3 months with no need for steroids or anti-epileptic medications.
  • Prior solid-organ transplantation.
  • Prior treatment with allogenic stem cell transplant ≤6 months before the first dose of study drug, has evidence of graft versus host disease, or requires immunosuppressant therapy.
  • Autologous HSCT within 3 months before the first dose of ETH-155008.
  • Active autoimmune disease within the past 2 years requires systemic immunosuppressive medications (ie, chronic corticosteroid, methotrexate, or tacrolimus).
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  • 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 1B or less.
  • Non-invasive basal cell or squamous cell skin carcinomas.
  • Non-invasive, superficial bladder cancer.
  • Prostate cancer with a current 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 CR of > 2 years duration.
  • Prior treatment with a CDK4/6 or Pim inhibitor.
  • Known allergies, hypersensitivity, or intolerance to ETH-155008 or its excipients.
  • Prior chemotherapy within 3 weeks prior to first treatment, targeted therapy, immunotherapy, radiotherapy, or treatment with an investigational anticancer agent (including investigational vaccines) within 2 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.
  • 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.
  • If corticosteroids were used to treat immune-related adverse events associated with prior therapy, ≥7 days must have elapsed since the last dose of corticosteroid.
  • History of clinically significant cardiovascular disease within the 6 months prior to the first dose of study drug including, but not limited to:
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  • 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; uncomplicated (Grade ≤2) deep vein thrombosis is not considered exclusionary.
  • Congestive heart failure (New York Heart Association class III-IV)
  • Pericarditis or clinically significant pericardial effusion
  • Myocarditis
  • Endocarditis 13. Clinically significant pulmonary compromise, particularly the need for supplemental oxygen to maintain adequate oxygenation.
  • 14. 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.
  • 15. Evidence of active viral, bacterial, or uncontrolled systemic fungal infection requiring parenteral treatment within 2 weeks before the first dose of study drug.
  • 16. 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 or without anti-HBs.
  • Hepatitis C infection is defined by a positive hepatitis C virus (HCV) ribonucleic acid (RNA).
  • 17. Tested HIV positive at screening. 18. 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.
  • 19. 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.
  • 20. Requires a prohibited medication that cannot be discontinued or substituted, or temporally interrupted during the study; see Section 6.6.2 for prohibited therapies.
  • 21. Are currently taking or have previously taken a sensitive oral CYP3A4 substrate or an oral 3A4 substrate with narrow therapeutic window (an at least 5 x half-life washout will be required).
  • 22. Are currently taking or have taken a potent CYP3A4 or p-glycoprotein inducer or inhibitors (inclusive of prescription and over-the-counter medication and/or herbal products). An at least 2-week (or at least 5 x half-life washout for long half-life products) will be required.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Australia5 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Alfred hospital

    Melbourne, Victoria, 3004

  • Peninsula and South Eastern Haematologuy and Oncology Group

    Melbourne, 3199

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Epworth HealthCare

    Richmond, Victoria, 3121

Other trials in Australia

About this study

Official title: A Phase 1a/1b Dose Escalation and Dose Expansion, First-in-human, Open-Labeled Study of ETH-155008 in Subjects With Relapsed or Refractory B-cell NHL, CLL/SLL and AML

This Trial is a FIH, open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ETH-155008 in subjects with R/R B-cell NHL, CLL/SLL and AML 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 PK and PD of ETH-155008 and preliminary clinical anti-tumor activity of ETH-155008 in subjects with R/R B-cell Non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) and acute myeloid leukemia (AML).

This Trial is a FIH, open-label, multicenter trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ETH-155008 in subjects with R/R B-cell NHL, CLL/SLL and AML 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 6 dose levels ranging from 10 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. Addition 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.

Conditions
NHL, Leukemia
Being tested
ETH-155008
Medical subject headings
Leukemia

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 NCT04840784
Study groupRoleWhat they receive
ETH-155008ExperimentalDose level: 10mg/day, 20mg/day, 40mg/day, 60mg/day, 80mg/day, 100mg/day. Each dose level will recruit 3-6 subjects, taking ETH-155008 tablets once daily.
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 relapsed/ refractory B-cell NHL, CLL/SLL and AML

    Measured: 4 weeks

  2. Incidence and severity of Serious Adverse Event (SAEs)

    Determine the safety of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML

    Measured: 4 weeks

  3. Dose Limiting Toxicity (DLTs)

    Incidence of DLTs starting from the first Dose period to the end of the first cycle of treatment of ETH-155008.

    Measured: 4 Weeks

  4. The RP2D(s) or the MTD of ETH-155008 in subjects with relapsed/ refractory B-cell NHL, CLL/SLL and AML

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

    Measured: 4 weeks

Secondary outcomes (8)

  1. PK parameter of ETH-155008: Cmax

    maximum Concentration (Cmax) of ETH-155008

    Measured: 3 months

  2. PK parameter of ETH-155008: Tmax

    Time of First Occurrence of Cmax for ETH-155008

    Measured: 4 weeks

  3. PK parameter of ETH-155008: AUC

    Area Under the Curve (AUC)

    Measured: 3months

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

    Inhibition of Pim kinases

    Measured: 6 months

  5. Assess the PD of ETH-155008: inhibition of FLT3

    inhibition of FLT3 (AML only)

    Measured: 6 months

  6. Assess the PD of ETH-155008: retinoblastoma protein

    Phosphorylation of upstream proteins: retinoblastoma protein (Rb)

    Measured: 6 months

  7. Assess the PD of ETH-155008:ribosomal protein

    Phosphorylation of upstream proteins: ribosomal protein (S6)

    Measured: 6 months

  8. Assess the PD of ETH-155008

    Signal transducer and activator of transcription 5 (Stat5) after treatment with study drug.

    Measured: 6 months

Timeline

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

  1. First posted12 Apr 2021
  2. Study start29 Jun 2021
  3. Primary completion2 May 2023
  4. Study completion2 May 2023

Why it stopped: The reasons for early termination is due to slow recruitment

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04840784
Sponsor's protocol ID
ETH-155008-101
Status last verified
May 2023
First submitted
5 Mar 2021
Last updated
11 Oct 2023
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 and Leukemia, run by Shengke Pharmaceuticals Pty Ltd at 5 sites in Australia.

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 36 inclusion and 42 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: stopped early, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Australia. 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?

The study was stopped early (reason given: The reasons for early termination is due to slow recruitment). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (time frame: 4 weeks). The study lists 4 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 NCT04840784.

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 11 Oct 2023.

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