Clinical Trial Finder

Inclusion Criteria:

1. Written informed consent. 2. Age 18-75 years (may be extended to older if deemed fit). 3. AML, ALL, DLBCL, Burkitt lymphoma, multiple myeloma or high-risk MDS, according to the WHO 2016 criteria. 4. The patient has received standard of care treatments and has refractory or relapsed disease with only experimental therapies as further treatment options. 5. Life expectancy of at least 8 weeks (as per investigators clinical assessment). 6. ECOG PFS 0-2. 7. Patients must have measurable disease by blood or bone marrow or imaging examination. 8. Adequate hepatic and renal function defined as: 1. Total bilirubin < 3 x ULN (does not apply to patients with Gilberts Syndrome). 2. AST and ALT ≤ 5 x ULN. 3. The calculated GFR is at least 30 ml/min using Cockcroft-Gault method. 9. Subject must be able to take oral medication. 10. Negative pregnancy test according to CTFG guidance 2014 for females of child-producing potential.

Exclusion Criteria:

1. Age less than 18 years. 2. 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. 3. Less than 3 weeks since stopping palliative radiotherapy. 4. Less than 3 weeks after surgery except access surgical procedures. 5. Less than 6 months since a clinically significant cardiovascular event such as myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke or TIA. 6. Congestive heart failure NYHA class >

• II. 7.

History of arrhythmias or arrhythmias discovered during the screening period (apart from atrial fibrillation without ventricular tachycardia and premature extra beats. 8. Patients requiring anti-arrhythmic drugs except for stable dose beta-blocking or calcium channel blocking agents. 9. QTc interval >470 ms at baseline (Fridericia correction). 10. Use of Fentanyl (must be stopped at least 1 week prior to initiation of Karonudib). 11. Use of anti-oxidants vitamins and Acetylcysteine (must be stopped within 48 hours of starting treatment with Karonudib). 12. Use of antidepressant medications which are substrate for CYP2D6 (must be stopped at least 3 weeks prior to starting treatment with Karonudib). 13. Any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of study results. 14. Intracerebral engagement (patient with previously known engagement are eligible provided that there is no evidence of disease progression for a minimum of 8 weeks prior to inclusion. 15. Known acute or chronic infection with hepatitis B or C except for DNA-negative hepatitis B with stable dose anti-viral agents. 16. Known HIV infection. 17. Pregnant or breast-feeding women. 18. Patients with reproductive potential not implementing accepted and effective means of contraception. 19. Participation in any other clinical trial with a pharmaceutical product within 10 x t½, or minimum 2 weeks, since last dosing of the IMP. 20. Acute promyelocytic leukemia (AML M3). 21. Uncontrolled ongoing systemic or localized infection. 22. Unable to comply with study procedures. 23. Peripheral neurological toxicity CTCAE grade 2 or higher.

Arms

Experimental: Dose escalation

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.

Interventions

Drug: - Karonudib

Dose escalation of administration with Karonudib. Three different dose cohorts are planned.