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Relapsed or Refractory Non-Hodgkin's LymphomaPhase 1NCT05965505

Study of AXT-1003 in Adult Subjects With Relapsed/Refractory Non-Hodgkin Lymphomas

A Phase 1 study testing AXT-1003 in people with Relapsed or Refractory Non-Hodgkin's Lymphoma, run by Axter Therapeutics (Beijing) Co., Ltd at 4 sites in China.

Terminated

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

Official record
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Trial summary

This is an open-label, multicenter, phase I study of AXT-1003 to assess the safety, tolerability, and pharmacokinetics in adult subjects with Relapsed/Refractory Non-Hodgkin Lymphomas. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AXT-1003
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
4 sitesChina
Study dates
11 Aug 2023to 5 Sep 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female or male subjects aged ≥ 18 years.
  • Histopathological diagnosis of relapsed/refractory non-Hodgkin lymphoma [R/R NHL] (except for CLL/SLL), who have progressed after treatment with approved therapies or who have no access to approved or standard therapies.
  • Note 1: Refractory is defined as failure to:
  • Achieve complete response after first-line therapy
  • Reach at least partial response after second-line therapy or beyond. Note 2: Subjects must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
  • For dose expansion part: Subjects with pathologically confirmed R/R NHL by the local pathologist/investigators are enrolled. Most of the enrolled subjects are confirmed with R/R PTCL subtype. Local histological diagnosis will be used for eligibility determination. Subjects with PTCL are eligible according to 2016 World Health Organization (WHO) classification, including but not limited to the following subtypes:
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  • PTCL, not otherwise specified.
  • Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) positive
  • Anaplastic large cell lymphoma, ALK negative
  • Angioimmunoblastic T-cell lymphoma
  • Extranodal NK-/T-cell lymphoma, nasal type The subjects enrolled in the dose expansion part should be progressed after treatment with approved therapies or who have no access to approved or standard therapies.
  • Eastern Cooperative Oncology Group performance status scale 0 to 1.
  • Have a life expectancy of at least 3 months.
  • Have measurable disease as defined by Lugano 2014 criteria, subjects must have measurable lesions (nodal lesion with any long diameter > 1.5 cm, or extranodal lesion with any long diameter > 1.0 cm) (not mandatory for the dose escalation stage).
  • Willing to provide archived or fresh tumor tissue samples that are sufficient for EZH2 status detection (not mandatory).
  • Adequate organ function assessed within 7 days prior to study drug administration.
  • Bone marrow function: absolute neutrophil count (ANC) ≥ 1.0 × 109/L without growth factor support (filgrastim or) for at least 14 days; Hb ≥ 9.0 g/dL (may receive transfusion), platelets ≥ 75 × 109/L (Evaluated after at least 7 days since last platelet transfusion).
  • Hepatic function: serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome; alkaline phosphatase (in the absence of bone disease) ALT/AST ≤ 3.0 × ULN (≤ 5 × ULN if subject has liver metastases).
  • Renal function: calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault method).
  • Time between prior anticancer therapy and first dose of AXT-1003 as below:
  • Cytotoxic chemotherapy-at least 21 days or 3.5 half-lives of prior treatment, whichever occurs later.
  • Non-cytotoxic chemotherapy (eg, small molecule inhibitor)-at least 14 days or 3.5 half-lives of prior treatment, whichever occurs later.
  • Nitrosoureas-At least 6 weeks or 3.5 half-lives of prior treatment, whichever occurs later.
  • Monoclonal antibody (ies)-at least 28 days
  • Radiotherapy-At least 14 days from local site radiation therapy/at least 6 weeks from prior radioisotope therapy/at least 12 weeks from 50% pelvic or total body irradiation.
  • High dose therapy with autologous hematopoietic cell infusion-at least 60 days.
  • High dose therapy with allogeneic transplant-At least 90 days (if graft versus host disease [GVHD] is present, must be Grade < 2) and no prohibited medications.
  • Note: Starting at Cycle 1 Day 1, subjects may receive no more than 10 mg of prednisone daily (or equivalent corticosteroid) when used for treatment of lymphoma related symptoms, with the intent to taper by the end of Cycle 1.
  • Male subjects must have had a successful vasectomy (with confirmed azoospermia), or they and their female partner must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception and use a condom throughout the study period and for 3 months after study drug discontinuation). Non-vasectomized male subjects must also agree to refrain from donating sperm from first dose of AXT-1003 until 3 months following the last dose of AXT-1003.
  • Females must not be lactating or pregnant at screening or baseline (as documented by a negative beta-human chorionic gonadotropin test with a minimum sensitivity of 25 IU/L or equivalent units of beta-human chorionic gonadotropin). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than seven days before the first dose of study drug. All females will be considered as childbearing potential unless they are postmenopausal (at least 12 months consecutively amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to randomization, during treatment cycles, and for 30 days (will be re estimated after PK profile is known) after the final dose of study drug and have a male partner who uses a condom. Highly effective contraception includes:
  • Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide.
  • Placement of an intrauterine device.
  • Established hormonal contraceptive methods: oral, injectable, or implant. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. Female subjects exempt from this requirement if they practice total abstinence or have a male partner who is vasectomized. If currently abstinent, the subject must agree to use a highly effective method of contraception as described above if they become sexually active during the treatment cycles, and for 30 days after study drug discontinuation.
  • Signed ICF and willing to comply with all aspects of the protocol.

Who cannot join

  • Diagnosis of precursor B-cell lymphoblastic leukemia/lymphoma, precursor T-cell lymphoblastic leukemia/lymphoma, precursor NK cell lymphoblastic leukemia/lymphoma.
  • Diagnosis of CLL, SLL.
  • Diagnosis of Burkitt lymphoma.
  • Received treatment with compounds with the same mechanism of action (EZH2 inhibitor, EZH1/EZH2 inhibitor etc.).
  • Central nervous system infiltration.
  • Clinically significant GVHD or GVHD requiring systemic immunosuppressive prophylaxis or treatment.
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  • Uncontrolled or significant cardiovascular disease, including:
  • Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QT corrected for heart rate using Fridericia's method > 470 msec) (average of triplicate determinations).
  • Diagnosed or suspected long QT syndrome or known family history of long QT syndrome.
  • History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
  • Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial fibrillation may be enrolled) or asymptomatic persistent ventricular tachycardia.
  • History of second- or third-degree heart block. Subjects with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers within 6 months prior to screening.
  • Myocardial infarction within 6 months prior to screening.
  • Angioplasty or stent craft implantation within 6 months prior to screening.
  • Uncontrolled angina pectoris within 6 months prior to screening.
  • New York Heart Association Class 3 or 4 congestive heart failure.
  • Coronary/peripheral artery bypass graft within 6 months prior to screening.
  • Uncontrolled hypertension (resting systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg).
  • Complete left bundle branch block.
  • Venous thrombosis or pulmonary embolism within the last 3 months before starting treatment.
  • Major surgery within 4 weeks before the first dose of study drug. Note: Minor surgery (e.g, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrolment.
  • Known or suspected hypersensitivity to AXT-1003 or any of the excipients.
  • Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of AXT-1003.
  • Use of known median or potent Cytochrome P450 3A4 (CYP3A4) inducers/inhibitors or P glycoprotein (P-gp) inhibitors.
  • Subjects unwilling to remove seville oranges, grapefruit juice and grapefruit from their diet.
  • History of other malignancies prior to enrolment; except for subjects with basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or other carcinomas in situ who have undergone possible curative treatment and do not have disease recurrence within 5 years since starting the treatment.
  • Any prior treatment-related (ie, chemotherapy, immunotherapy, radiotherapy, target therapy or other study clinical therapy) clinically significant toxicities that have not resolved to Grade ≤ 1 per CTCAE version 5.0 or prior treatment-related toxicities that are clinically unstable and clinically significant at time of enrolment.
  • Active infection requiring systemic therapy.
  • Has known history of chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (detectable antihepatitic C circulating viral RNA).
  • Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus, and tuberculosis.
  • Females who are pregnant or breastfeeding.
  • Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.

Trial locations and contacts

4 sites in 1 country.

China4 sites
  • Beijing Cancer Hospital

    Beijing

  • West China Hospital, Sichuan University

    Chengdu

  • Sun Yat-sen University Cancer Center

    Guangzhou

  • Tianjin Medical University Cancer Institute & Hospital

    Tianjin

Other trials in China

About this study

Official title: An Open-Label, Multicenter, Phase I Study of AXT-1003 as a Single Agent in Adult Subjects With Relapsed/Refractory Non-Hodgkin Lymphomas

This is an open-label, multicenter, phase I study of AXT-1003 to assess the safety, tolerability, and pharmacokinetics in adult subjects with Relapsed/Refractory Non-Hodgkin Lymphomas.

Read the detailed description

The study is being conducted to assess the safety, tolerability, and pharmacokinetics (PK) of AXT-1003 in subjects with relapsed/refractory non-Hodgkin lymphomas (R/R NHL) and relapsed/refractory peripheral T-cell lymphoma (R/R PTCL), a subtype of R/R NHL.

Being tested
AXT-1003
Keywords
NHL, EZH2 inhibitor, Phase I, Peripheral T-cell Lymphoma
Medical subject headings
Recurrence, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell, Peripheral

What participants receive

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

  • AXT-1003Drug

    AXT-1003 capsule is administered orally daily, until disease progression or intolerable toxicity.

Study groups in NCT05965505
Study groupRoleWhat they receive
AXT-1003ExperimentalDose Escalation: Level 1 (Starting Dose) Oral AXT-1003 100 mg BID; Level 2 Oral AXT-1003 200mg BID; Level 3 Oral AXT-1003 300mg BID ; Level 4 Oral AXT-1003 450mg BID; Level 5 Oral AXT-1003 600mg BID; Level 6 Oral AXT-1003 750mg BID Dose Expansion: 1 or 2 cohorts at the dose levels selected from dose escalation part
Receives: Drug: AXT-1003

What is being measured

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

  1. Number of Participants With Dose-Limiting Toxicity (DLT) (Dose Escalation)

    Dose Escalation only: to characterize the dose limiting toxicities (DLTs) of AXT-1003.

    Measured: Up to 28 days

  2. Number of Participants with Adverse Events (AEs) by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study treatment.

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Participants with multiple occurrences of an AE within a category were counted once within the category. Relatedness to study drug was assessed by the investigator.

    Measured: Baseline up to 30 days after the last dose of study drug

  3. Number of Participants with Clinically Significant Change from Baseline in Laboratory Abnormalities by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

    Laboratory parameters included: hematology, blood chemistry, urinalysis and coagulation. Clinical significance of laboratory parameters was determined at the investigator's discretion.

    Measured: Baseline up to 30 days after the last dose of study drug

Secondary outcomes (13)
  1. Overall response rates (ORR)

    ORR is defined as the proportion of subjects with a CR or PR.

    Measured: Up to 3 years

  2. Duration of response(DOR)

    DOR is defined as the time from the initial objective response to progression of disease (PD) or death after the response, whichever occurs first.

    Measured: Up to 3 years

  3. Progression free survival (PFS)

    Progression-free survival is defined as the time from the first dose of study treatment to the first PD or death for any reason in the absence of documented PD, whichever occurs first

    Measured: Up to 3 years

  4. Time to response (TTR)

    Time to response is defined as the time from first dose of study treatment to the first objective tumor response.

    Measured: Up to 3 years

  5. Disease control rate (DCR)

    Disease control rate is defined as the proportion of subjects with a CR, PR, or stable disease(SD).

    Measured: Up to 3 years

  6. Maximum observed concentration (Cmax) of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 15 days

  7. Time of maximum observed concentration (tmax) of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 15 days

  8. Area under the curve from the time of dosing to the time of the last measurable concentration (AUC0-t) of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 15 days

  9. The partial area from dosing time to dosing time plus Tau (AUC0-tau) of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 15 days

  10. Trough concentration of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 5 months

  11. Minimum observed concentration (Cmin) of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 15 days

  12. Terminal elimination half-life (t1/2) of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 15 days

  13. Total body clearance (CL/F) of AXT-1003

    Pharmacokinetics of AXT-1003

    Measured: Up to 15 days

Timeline

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

  1. First posted28 Jul 2023
  2. Study start11 Aug 2023
  3. Primary completion5 Sep 2023
  4. Study completion5 Sep 2023

Why it stopped: Due to the adjustment of the protocol and expansion of the indication population, a new clinical trial protocol was submitted to the Health Authority, so the registration was conducted as a new clinical trial and this trial was terminated.

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
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05965505
Sponsor's protocol ID
AXT1003-1101
Other IDs
CTR20231973
Status last verified
Jul 2023
First submitted
12 Jul 2023
Last updated
1 Aug 2024
Results posted
No
Data monitoring committee
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 AXT-1003 in people with Relapsed or Refractory Non-Hodgkin's Lymphoma, run by Axter Therapeutics (Beijing) Co., Ltd at 4 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 34 inclusion and 32 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 1 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

The study was stopped early (reason given: Due to the adjustment of the protocol and expansion of the indication population, a new clinical trial protocol was submitted to the Health Authority, so the registration was conducted as a new clinical trial and this trial was terminated.). 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?

Number of Participants With Dose-Limiting Toxicity (DLT) (Dose Escalation) (time frame: Up to 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?
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 1 Aug 2024.

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