Status:
RECRUITING
A Study in Leukemia Patients With Karonudib
Lead Sponsor:
Thomas Helleday Foundation
Conditions:
Leukemia
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
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 ...
Detailed Description
Primary Objective Part I * To determine the safety and tolerability of Karonudib in escalating doses for the treatment of patients with advanced relapsed/refractory Acute Myeloid Leukemia (AML), Acut...
Eligibility Criteria
Inclusion
- 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.
- The calculated GFR is at least 30 ml/min using Cockcroft-Gault method.
- Platelet count≥10 x 109/L. (Can be supported by platelet transfusion)
- Subject must be able to take oral medication.
- Negative pregnancy test according to CTFG guidance 2014 for females of child-producing potential.
Exclusion
- 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.
- 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.
- 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.
- Pregnant or breast-feeding women.
- Patients with reproductive potential not implementing accepted and effective means of contraception.
- Participation 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.
- Acute promyelocytic leukemia (AML M3).
- Uncontrolled ongoing systemic or localized infection.
- Unable to comply with study procedures.
- Peripheral neurological toxicity CTCAE grade 2 or higher.
Key Trial Info
Start Date :
December 3 2019
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 30 2026
Estimated Enrollment :
9 Patients enrolled
Trial Details
Trial ID
NCT04077307
Start Date
December 3 2019
End Date
December 30 2026
Last Update
December 19 2025
Active Locations (6)
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1
Aarhus University Hospital
Aarhus, Denmark
2
Rigshospitalet Copenhagen University Hospital
Copenhagen, Denmark
3
University Clinical Center Belgrade
Belgrade, Serbia
4
University Clinical Center Kragujevac
Kragujevac, Serbia