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A Study in Leukemia Patients With Karonudib (MAATEO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04077307
Recruitment Status : Recruiting
First Posted : September 4, 2019
Last Update Posted : February 4, 2021
Sponsor:
Information provided by (Responsible Party):
Thomas Helleday Foundation

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.


Condition or disease Intervention/treatment Phase
Leukemia Drug: Karonudib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: 3 different dose cohorts with escalating doses are planned.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study in Patients With Hematological Malignancies to Evaluate Safety, Tolerability and Efficacy of Karonudib
Actual Study Start Date : December 3, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
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.
Drug: Karonudib
Dose escalation of administration with Karonudib. Three different dose cohorts are planned.




Primary Outcome Measures :
  1. Safety of Karonudib (TH1579) [ Time Frame: 28 days, first treatment cycle for the patient. ]
    Grade and frequency of AE and SAE using the CTCAE version 5.0

  2. Tolerability of Karonudib (TH1579) [ Time Frame: 28 days, first treatment cycle for the patient. ]
    Grade and frequency of AE and SAE using the CTCAE version 5.0


Secondary Outcome Measures :
  1. Preliminary signs of clinical efficacy of Karonudib. [ Time Frame: 28 days, first treatment cycle for the patient. ]
    ELN/IWG response criteria



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04077307


Contacts
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Contact: Teresa Sandvall, MSc +46737121239 teresa.sandvall@oxcia.se

Locations
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Sweden
Karolinska University Hospital Recruiting
Huddinge, Sweden
Contact: Stefan Deneberg, MD, PhD         
Principal Investigator: Stefan Deneberg, MD, PhD         
Sponsors and Collaborators
Thomas Helleday Foundation
Investigators
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Principal Investigator: Stefan Deneberg, MD Karolinska University Hospital
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Responsible Party: Thomas Helleday Foundation
ClinicalTrials.gov Identifier: NCT04077307    
Other Study ID Numbers: MAATEO
First Posted: September 4, 2019    Key Record Dates
Last Update Posted: February 4, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Thomas Helleday Foundation:
AML
ALL
MDS
Multiple myeloma
B cell lymphoma
Additional relevant MeSH terms:
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Leukemia
Neoplasms by Histologic Type
Neoplasms