TH1579 for Hematological malignancies | Acute myeloid leukemia (AML) | Acute lymphoblastic leukemia (ALL) | Diffuse large B-cell lymphoma (DLBCL) | Burkitt lymphoma | Multiple myeloma | Myelodysplastic syndrome (high-risk)

Inclusion criteria

• {"criterion_text":"- 1.\tWritten informed consent.\n- 2.\tAge 18-75 years (may be extended to older if deemed fit).\n- 3.\tThe 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.\n- 4.\tCohorts I-IV: AML, ALL, DLBCL, Burkitt lymphoma, multiple myeloma or high-risk MDS, according to the WHO 2016 criteria. Expansion cohort (Cohort V): AML or MDS according to the ELN 2017 criteria.\n- 5.\tLife expectancy of at least 8 weeks (as per investigators clinical assessment).\n- 6.\tECOG PFS 0-2\n- 7.\tPatients must have measurable disease by blood or bone marrow or imaging examination.\n- 8.\tHave a normal left ventricular ejection fraction (LVEF) based on institutional ranges.\n- 9.\tAdequate hepatic and renal function defined as: a.\tTotal bilirubin < 3 x ULN (does not apply to patients with Gilberts Syndrome). b.\tAST and ALT ≤ 5 x ULN. c.\tThe calculated GFR is at least 30 ml/min using Cockcroft-Gault method.\n- 10.\tPlatelet count≥10 x 109/L. (Can be supported by platelet transfusion)\n- 11.\tSubject must be able to take oral medication. Negative pregnancy test according to CTFG guidance 2014 for females of child-producing potential."}

Exclusion criteria

• {"criterion_text":"- 1.\tAge less than 18 years.\n- 2.\tLess than 4 weeks since stopping previous systemic chemotherapy treatment with the exception of Hydroxyurea, Trophosphamide, oral Cyclophosphamide, ImID or Thioguanine which needs to be stopped 10 x t1/2 prior to Karonudib administration.\n- 3.\tLess than 1 week since stopping palliative radiotherapy.\n- 4.\tLess than 2 weeks after surgery except access surgical procedures.\n- 5.\tLess than 6 months since a clinically significant cardiovascular event such as myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke or TIA.\n- 6.\tCongestive heart failure NYHA class > II.\n- 7.\tHistory of arrhythmias or arrhythmias discovered during the screening period (apart from atrial fibrillation without ventricular tachycardia and premature extra beats).\n- 8.\tPatients requiring anti-arrhythmic drugs except for stable dose beta-blocking or calcium channel blocking agents.\n- 9.\tQTc interval >470 ms at baseline (Fridericia correction).\n- 10.\tUse of Fentanyl (must be stopped at least 1 week prior to initiation of Karonudib).\n- 11.\tUse of anti-oxidants vitamins and Acetylcysteine (must be stopped within 48 hours of starting treatment with Karonudib).\n- 12.\tUse of antidepressant medications which are substrate for CYP2D6 (must be stopped at least 3 weeks prior to starting treatment with Karonudib).\n- 13.\tAny severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of study results.\n- 14.\tIntracerebral 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.\n- 15.\tKnown acute or chronic infection with hepatitis B or C except for DNA-negative hepatitis B with stable dose anti-viral agents.\n- 16.\tKnown HIV infection.\n- 17.\tPregnant or breast-feeding women.\n- 18.\tPatients with reproductive potential not implementing accepted and effective means of contraception.\n- 19.\tParticipation in any other clinical trial with a pharmaceutical product within 5 x t½, or minimum 1 week, since last dosing of the IMP, whichever is the shorter.\n- 20.\tAcute promyelocytic leukemia (AML M3).\n- 21.\tUncontrolled ongoing systemic or localized infection.\n- 22.\tUnable to comply with study procedures.\n- 23.\tPeripheral neurological toxicity CTCAE grade 2 or higher."}

Primary endpoints

• {"endpoint_text":"- Primary Objective Part I •\tTo determine the safety and tolerability of Karonudib in escalating doses for the treatment of patients with advanced relapsed/refractory Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL) , Diffuse Large B-Cell Lymphoma, Multiple Myeloma (MM) and high-risk Myelodysplastic Syndrome (MDS) Primary Objective Part II To determine the safety and tolerability of Karonudib in combination with other anti-cancer agents for the treatment of patients with advance","definition_or_measurement_approach":"Safety and tolerability to be determined in a dose-escalation design; secondary objectives state determination of DLT and MTD, recommended phase 2 dose (RP2D), and pharmacokinetics, which indicates assessment via dose-limiting toxicities (DLTs), MTD determination, adverse event reporting and PK measurements."}

Sweden

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

699

Number Of Sites

1

Number Of Participants

25

Denmark

Earliest CTIS Part Ii Submission Date

19-02-2025

Latest Decision Or Authorization Date

12-03-2026

Processing Time Days

386

Number Of Sites

2

Number Of Participants

6

Primary sponsor

Full Name

Oxcia AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

CTC Clinical Trial Consultants AB

Responsibilities

Listed as third party with sponsor duties (code: 1) and contact/email provided (ulrika.amador@ctc-ab.se).

Third parties

• {"country":"Sweden","full_name":"CTC Clinical Trial Consultants AB","duties_or_roles":"sponsorDuties codes: 1 (as listed in CTIS thirdParties)","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Oxcia AB","duties_or_roles":"sponsorDuties codes: 10,11,12,13,14,2,4,5,6,7,8,9 (as listed in CTIS thirdParties)","organisation_type":"Pharmaceutical company"}

Co-sponsors

• Thomas Helledays Stiftelse Foer Medicinsk Forskning
• Oxcia AB