A Study in Leukemia Patients With Karonudib

NCT04077307 | Recruiting Phase 1 DMC

• 1 other identifier: MAATEO
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 4

Brief Summary

The primary objective of this study is to determine safety and tolerability of Karonudib for the treatment of hematological malignancies. Secondary objectives are to determine a recommended RP2D and schedule for further development of Karonudib, to determine the pharmacokinetics of Karonudib, to look for evidence of treatment efficacy. Overall survival will also be recorded.

Conditions

Leukemia

Keywords

AML; ALL; MDS; Multiple myeloma; B cell lymphoma

Outcome Measures

Primary Outcomes (2)

• Safety of Karonudib (TH1579)

  Grade and frequency of AE and SAE using the CTCAE version 5.0

  28 days, first treatment cycle for the patient.

• Tolerability of Karonudib (TH1579)

  Grade and frequency of AE and SAE using the CTCAE version 5.0

  28 days, first treatment cycle for the patient.

Secondary Outcomes (1)

• Preliminary signs of clinical efficacy of Karonudib.

  28 days, first treatment cycle for the patient.

Study Arms (1)

Dose escalation

EXPERIMENTAL

Karonudib is an oral inhibitor of MTH1 and will be supplied as an oral solution to be taken every other day. There are three planned dose cohorts. Patients will be given every second day dosing.

Drug: Karonudib

Interventions

Karonudib DRUG

First part of the study - four different dose cohorts Extension part of the study - karonudib BID (twice a week) and Idarubicin days 1-3.

Dose escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Age 18-75 years (may be extended to older if deemed fit).
• The patient has received standard of care treatments and has refractory or relapsed or progressive disease with no suitable standard of care options available.
• For expansion cohort (Cohort V): Patients can only have received a maximum of 70% of anthracycline lifetime exposure to date of proposed dosing day.
• Cohorts I-IV: AML, ALL, DLBCL, Burkitt lymphoma, multiple myeloma or high-risk MDS, according to the WHO 2016 criteria.
• Expansion cohort (Cohort V): Relapsed, Recurrent or Progressive AML or MDS according to the ELN 2017 criteriaWHO 2016 criteria.
• For expansion cohort (Cohort V): Patients can only have received a maximum of 70% of anthracycline lifetime exposure to date of proposed dosing day.
• The patient has received standard of care treatments and has refractory or relapsed disease with only experimental therapies as further treatment options.
• Life expectancy of at least 8 weeks (as per investigators clinical assessment).
• ECOG PFS 0-2
• Patients must have measurable disease by blood or bone marrow or imaging examination.
• Have a normal left ventricular ejection fraction (LVEF) based on institutional ranges.
• Adequate hepatic and renal function defined as:
• Total bilirubin \< 3 x ULN (does not apply to patients with Gilberts Syndrome).
• AST and ALT ≤ 5 x ULN.

You may not qualify if:

• Age less than 18 years.
• Less than 4 weeks since stopping previous systemic chemotherapy treatment with the exception of stable dose Hydroxyurea, Trophosphamide, oral Cyclophosphamide, ImID or Thioguanine which needs to be stopped 10 x t1/2 prior to Karonudib administration.
• Less than 1 week since stopping palliative radiotherapy.
• Less than 2 weeks after surgery except access surgical procedures.
• Less than 6 months since a clinically significant cardiovascular event such as myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke or TIA.
• Congestive heart failure NYHA class \> II.
• History of arrhythmias or arrhythmias discovered during the screening period (apart from atrial fibrillation without ventricular tachycardia and premature extra beats).
• Patients requiring anti-arrhythmic drugs except for stable dose beta-blocking or calcium channel blocking agents.
• QTc interval \>470 ms at baseline (Fridericia correction).
• Use of Fentanyl (must be stopped at least 1 week prior to initiation of Karonudib).
• Use of anti-oxidants vitamins and Acetylcysteine (must be stopped within 48 hours of starting treatment with Karonudib).
• Use of antidepressant medications which are substrate for CYP2D6 (must be stopped at least 3 weeks prior to starting treatment with Karonudib).
• Any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of study results.
• Known acute or chronic infection with hepatitis B or C except for DNA-negative hepatitis B with stable dose anti-viral agents.
• Known HIV infection.

Sponsors & Collaborators

• Thomas Helleday Foundation: lead

Study Sites (6)

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Rigshospitalet Copenhagen University Hospital

Copenhagen, Denmark

RECRUITING

University Clinical Center Belgrade

Belgrade, Serbia

RECRUITING

University Clinical Center Kragujevac

Kragujevac, Serbia

RECRUITING

Karolinska University Hospital

Huddinge, Sweden

RECRUITING

Örebro University Hospital

Örebro, Sweden

RECRUITING

MeSH Terms

Conditions

Leukemia; Multiple Myeloma; Lymphoma, B-Cell

Interventions

karonudib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Lymphatic Diseases

Study Officials

• Stefan Deneberg, MD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Klockare, BSc

CONTACT

+46706232505; maria.klockare@oxcia.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: First part of the study - 3 different dose cohorts with escalating doses are planned. Extension part of the study - 20 patients with diagnosis of Relapsed, Refractory or Progressive AML and MDS to be enrolled and treated with RP2D.

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: September 4, 2019
• Study Start: December 3, 2019
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); DK (2)