MAATEO: A phase 1 study in patients with hematological malignancies to evaluate safety, tolerability and efficacy of Karonudib

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oxcia AB, Thomas Helledays Stiftelse Foer Medicinsk Forskning, Oxcia AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

3 Dec 2019 → ongoing

Decision date (initial)

2025-03-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513766-20-00

EudraCT number

2019-001221-27

ClinicalTrials.gov

NCT04077307

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To 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

To determine the safety and tolerability of Karonudib in combination with other anti-cancer agents for the treatment of patients with advanced progressive, relapsed/refractory AML, and high-risk MDS

Secondary objectives 1

1. • To determine a recommended phase 2 dose (RP2D) and schedule for Karonudib. • To define DLT and MTD. • To determine the pharmacokinetics of Karonudib. • To determine preliminary signs of clinical efficacy.

Conditions and MedDRA coding

Hematological malignancies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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. 4. Cohorts 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. 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. Have a normal left ventricular ejection fraction (LVEF) based on institutional ranges. 9. Adequate hepatic and renal function defined as: a. Total bilirubin < 3 x ULN (does not apply to patients with Gilberts Syndrome). b. AST and ALT ≤ 5 x ULN. c. The calculated GFR is at least 30 ml/min using Cockcroft-Gault method. 10. Platelet count≥10 x 109/L. (Can be supported by platelet transfusion) 11. Subject must be able to take oral medication. Negative pregnancy test according to CTFG guidance 2014 for females of child-producing potential.

Exclusion criteria 1

1. 1. Age less than 18 years. 2. Less 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. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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), 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oxcia AB

Sponsor organisation

Oxcia AB

Address

Norrbackagatan 70 C, St Matteus St Matteus

City

Stockholm

Postcode

113 34

Country

Sweden

Scientific contact point

Organisation

Oxcia AB

Contact name

Ulrika Warpman Berglund

Public contact point

Organisation

Oxcia AB

Contact name

Ulrika Warpman Berglund

Third parties 2

Thomas Helledays Stiftelse Foer Medicinsk Forskning

Sponsor organisation

Thomas Helledays Stiftelse Foer Medicinsk Forskning

Address

Fogdevreten 2a

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Thomas Helledays Stiftelse Foer Medicinsk Forskning

Contact name

Ulrika Warpman Berglund

Public contact point

Organisation

Thomas Helledays Stiftelse Foer Medicinsk Forskning

Contact name

Ulrika Warpman Berglund

Third parties 1

Oxcia AB

Sponsor organisation

Oxcia AB

Address

Norrbackagatan 70 C, St Matteus St Matteus

City

Stockholm

Postcode

113 34

Country

Sweden

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications