A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies
Leukemia, Myeloid, Acute
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of AML according to World Health Organization (WHO) 2016 criteria a) De novo or secondary AML; b) relapsed /refractory (Arm A); c) harboring NPM1 / KMT2A alterations
- Pretreatment clinical laboratory values meeting the following criteria -listed below: White blood cell (WBC) count: less than or equal to <=25 x 10^9 per liter (/L), adequate liver and renal function
- ECOG performance status grade of 0, 1 or 2
- A woman of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment
- Must sign an informed consent form (ICF) indicating participant understands the purpose of the study and procedures required for the study and is willing to participate in the study.
- Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion Criteria:
- Acute promyelocytic leukemia according to WHO 2016 criteria
- Leukemic involvement of the central nervous system
- Recipient of solid organ transplant
- Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or that was diagnosed within 6 months prior to the first dose of study treatment including, but not limited to:(a) Myocardial infarction; (b) Severe or unstable angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (less than [<] 50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example, blood pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute neurologic events such as stroke or transient ischemic attack, intracranial or subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events (example, pulmonary embolism) within 1 month prior to the first dose of study treatment (uncomplicated Grade less than or equal to [≤]2 deep vein thrombosis is not considered exclusionary);(g)Congestive heart failure (NYHA class III to IV); (h) Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j) Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia (corrected for hypoalbuminemia)
- 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
- Pulmonary compromise that requires the need for supplemental oxygen use to maintain adequate oxygenation
Sites / Locations
- The University of Alabama at BirminghamRecruiting
- City of HopeRecruiting
- Massachusetts General HospitalRecruiting
- Albert Einstein College Of MedicineRecruiting
- Novant HealthRecruiting
- Novant Health Forsyth Medical CenterRecruiting
- MD AndersonRecruiting
- Monash Medical CentreRecruiting
- Peter MacCallum Cancer CentreRecruiting
- Westmead HospitalRecruiting
- Institut Paoli CalmettesRecruiting
- Institut Universitaire du Cancer Toulouse OncopoleRecruiting
- CHU de Tours - Hôpital de BretonneauRecruiting
- Charité Universitätsmedizin BerlinRecruiting
- Universitätsklinikum Carl Gustav Carus DresdenRecruiting
- Universitaetsklinikum HeidelbergRecruiting
- Universitaetsklinikum LeipzigRecruiting
- Universitatsklinikum UlmRecruiting
- Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di BolognaRecruiting
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriRecruiting
- ASST Grande Ospedale Metropolitano NiguardaRecruiting
- IRCCS Istituto Clinico HumanitasRecruiting
- Hosp. de La Santa Creu I Sant PauRecruiting
- Hosp. Clinic I Provincial de BarcelonaRecruiting
- Hosp. Univ. Vall D HebronRecruiting
- Hosp. Univ. Fund. Jimenez DiazRecruiting
- Clinica Univ. de NavarraRecruiting
- University College London Hospitals NHSFTRecruiting
- Christie Hospital NHS TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Arm A: Relapsed/Refractory Setting
Arm B: Newly Diagnosed Chemotherapy Ineligible Setting
Arm C: Newly Diagnosed Chemotherapy Eligible Setting
Participants with relapsed/refractory AML harboring either NPM1 or KMT2A alterations will receive JNJ-75276617 in combination with either venetoclax (VEN) (Cohort A1: JNJ75276617+VEN) or azacitidine (AZA) (Cohort A2: JNJ-75276617+AZA) or VEN+AZA (Cohort A3: JNJ-75276617+VEN+AZA) to select the recommended phase 2 dose (RP2D) of JNJ-75276617 in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive JNJ-75276617 in combination with AML directed therapies at the RP2D(s).
Participants will receive JNJ-75276617 in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring either KMT2A or NPM1 alterations who are greater than or equal to (>=) 75 years of age or >=18 to less than (<) 75 years of age with comorbidities that preclude the use of intensive induction chemotherapy.
Participants will receive combination of JNJ-75276617 with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants >=18 to <75 years of age with AML harboring either NPM1 or KMT2A alterations and eligible for intensive chemotherapy.