Karonudib treatment for leukemia patients

A Phase 1 Study in Patients With Hematological Malignancies to Evaluate Safety, Tolerability and Efficacy of Karonudib

This study is testing a new treatment called Karonudib for people with advanced leukemia and multiple myeloma to see if it is safe and works better alone or with other standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Thomas Helleday Foundation (Academic / other)
• Drugs / interventions: chemotherapy, Cyclophosphamide
• Locations: 6 sites (Aarhus and 5 other locations)
• Trial ID: NCT04077307 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and tolerability of Karonudib in patients with advanced relapsed or refractory hematological malignancies, including Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), and Multiple Myeloma. The study will assess Karonudib both as a standalone treatment and in combination with standard care therapies. It will also investigate the pharmacokinetics of Karonudib and gather evidence of its efficacy, with overall survival being a key outcome measure.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with relapsed or refractory leukemia who have exhausted standard treatment options.

Not a fit: Patients with early-stage leukemia or those who have not yet received standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat leukemia.

How similar studies have performed: Other studies have shown promise with similar approaches in treating hematological malignancies, but this specific treatment is novel.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent.
2. Age 18-75 years (may be extended to older if deemed fit).
3. 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.
4. Expansion cohort (Cohort V): Relapsed, Recurrent or Progressive AML or MDS according to the ELN 2017 criteriaWHO 2016 criteria.
5. For expansion cohort (Cohort V): Patients can only have received a maximum of 70% of anthracycline lifetime exposure to date of proposed dosing day.
6. The patient has received standard of care treatments and has refractory or relapsed disease with only experimental therapies as further treatment options.
7. Life expectancy of at least 8 weeks (as per investigators clinical assessment).
8. ECOG PFS 0-2
9. Patients must have measurable disease by blood or bone marrow or imaging examination.
10. Have a normal left ventricular ejection fraction (LVEF) based on institutional ranges.
11. 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.
12. Platelet count≥10 x 109/L. (Can be supported by platelet transfusion)
13. Subject must be able to take oral medication.
14. 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 1 week since stopping palliative radiotherapy.
4. Less than 2 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 5 x t½, or minimum 1 week, since last dosing of the IMP, whichever is the shorter.
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.

Where this trial is running

Aarhus and 5 other locations

• 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)

Study contacts

• Principal investigator: Stefan Deneberg, MD — Karolinska University Hospital
• Study coordinator: Maria Klockare, BSc

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