Medical condition: Acute leukaemia Medical condition in lay language: Blood cancer Therapeutic areas: Diseases [C] - Cancer [C04] Cancer
Conditions
Interventions
The study consists of:
1. Screening phase (up to 30 days)
2. Open-label treatment phase (up to 28 days): Participants will receive a single oral dose of 14C-bleximenib on Day 1. On Day 2, participants
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. =18 years of age and with a body weight of = 40 kg. 2. R/R acute leukaemia harbouring KMT2Ar (eg, gene rearrangement/translocation), NPM1m(eg, Exon 12 frameshift), or nucleoporin (NUP98 or NUP214, eg, gene rearrangement/translocation) alterations and has exhausted, or is ineligible for available therapeutic options. 3. Pretreatment clinical laboratory values meeting the following criteria: White blood cell (WBC) count =20 x 109/L; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × upper limit of normal (ULN); Total bilirubin =1.5 × ULN; Renal function Estimated or measured glomerular filtration rate =60 mL/min per four variable MDRD equation 4. ECOG performance status grade of 0 or 1 (Oken 1982) 5. Regular bowel movements (i.e., average production of at least one stool every 2 days). 6. A woman of childbearing potential must have a negative highly sensitive serum ß-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment. 7. A woman of childbearing potential must agree to all the following during the study and for 6 months after the last dose of study treatment: 7.1. Use a barrier method of contraception 7.2. Use a highly effective, preferably user-independent method of contraception 7.3. Not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction 7.4. Not planning to become pregnant 7.5. Not to breast-feed 8. A male must agree to all the following during the study and for 90 days after the last dose of study treatment: 8.1. Wear a condom when engaging in any activity that allows for the passage of ejaculate to another person. 8.2. Not to donate sperm or freeze for future use for the purpose of reproduction. 8.3. In addition, the participant should be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak. 9. Must sign an informed consent form (ICF) indicating participant (or their LAR) understands the purpose of the study and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of the standard of care for the participant’s disease. 10. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
Exclusion criteria
Exclusion criteria: 1. Acute promyelocytic leukemia or diagnosis of Down syndrome associated leukemia, according to WHO 2016 criteria (Arber 2016). 2. Active CNS disease. 3. Recipient of solid organ transplant. 4. Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes, or that was diagnosed within 6 months prior to Day1. 5. QTc according to Fridericia’s formula (QTcF) for males =450 msec or for females =470 msec. Participants with a family history of Long QT syndrome are excluded. 6. Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia, neutropenia, anemia) from previous anticancer therapy that has not resolved to baseline or to Grade 1 or less. 7. Pulmonary compromise that requires the need for supplemental oxygen use to maintain adequate oxygenation. 8. Reported temperature >100.4ºF/38ºC within 48 hours prior to study Day 1. 9. Known allergies, hypersensitivity, or intolerance to bleximenib or its excipients (refer to IB). 10. Exclusion criteria related to stem cell transplant: prior treatment with allogenic bone marrow or stem cell transplant =3 months before first dose of study treatment; evidence of graft versus host disease; received donor lymphocyte infusion =1 month before first dose of study treatment; requires immunosuppressant therapy (exception: daily doses =10 mg prednisone or equivalent are allowed for adrenal replacement). 11. Any prior treatment with a menin-KMT2A inhibitor. (Participants with R/R acute leukemia and prior menin-KMT2Ainhibitor exposure, without prior evidence of DS, may be considered with Sponsor approval with proper washout.) 12. Prior cancer immunotherapy (ie, CAR-T, inotuzumab, gemtuzumab ozogamicin) within 4 weeks prior to enrollment or blinatumomab within 2 weeks prior to enrollment. Additional prior cancer therapies must not be given within 2 weeks prior to enrollment or 5 half-lives of the agent (whichever is shorter). 13. Administration of: live-attenuated vaccine within 4 weeks before the first dose of study treatment or planned during study treatment; or investigational vaccine within 2 weeks before the first dose of study treatment. 14. Received investigational treatment or used an invasive investigational medical device within 2 weeks before planned first dose of study treatment or is currently receiving active treatment on an investigational study. 15. Major surgery (eg, requiring general anesthesia) within 2 weeks prior to first dose of study treatment or has not recovered from surgery. Must not have major surgery planned during the time the participant is receiving study treatment. 16. Requires prohibited medication that cannot be discontinued or substituted or temporally interrupted during the study. 17. Known to be positive or tests positive at screening for human immunodeficiency virus (HIV), unless viral load is undetectable and CD4 count is above 200 in stable highly active antiretroviral therapy (see Section 6.9.2 for prohibited and restricted medications) 18. Active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (as defined below) or clinically active infectious liver disease: 18.1. Positive hepatitis B surface antigen (HBsAg). NOTE: Participants with a prior history of hepatitis B virus (HBV) demonstrated by positive hepatitis B core antibody are eligible if they have at screening 1) a negative HbsAg and 2) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Participants with a positive HBs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of Dose Excreted in Urine (feu) - Total amount excreted into the urine, expressed as a percentage of the administered dose, will be reported up to day 28 2. Percentage of Dose Excreted in Feces (fef) - Total amount excreted into the feces expressed as a percentage of the administered dose, will be reported up to day 28 3. Amount Excreted in Urine (Aeu) - Aeu defined as the total amount of bleximenib and radioactivity excreted into the urine, and will be reported up to day 28 4. Amount Excreted in Feces (Aef) - Aef defined as the total amount of bleximenib and radioactivity excreted into the feces, and will be reported up to day 28 5. Area Under the Concentration-Time Curve from Time 0 to the Last Measurable Concentration (AUC0-t) - AUC0-t in whole blood and plasma will be reported on Cycle 1 Day 1, and Cycle 1 Day 2 (Cycle duration=28 days) 6. Maximum Observed Concentration (Cmax) - Maximum observed concentration in whole blood and plasma will be determined on Cycle 1 Day 1, and Cycle 1 Day 2 (Cycle duration=28 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using electronic Case Report Forms (eCRF) up to 58 days | — |
Countries
England, United Kingdom
Contacts
Public ContactAakta Al-Naqdi
Outcome results
None listed