A Study of JNJ-74856665 in Participants With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) (DHODH)
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- A diagnosis of: Arms A and C: Acute Myeloid Leukemia (AML) according to the World Health Organization (WHO) 2016 criteria with relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options; or newly transformed secondary AML according to the WHO 2016 criteria and have exhausted standard therapeutic options for AML during their treatment prior to transformation; or high-risk or very high-risk Myelodysplastic Syndrome (MDS) according to the WHO 2016 criteria and the revised International Prognostic Scoring System (IPSS-R) with relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options; or Arm A only: chronic myelomonocytic leukemia-2 (CMML-2) according to the WHO 2016 criteria with relapsed or refractory disease and have exhausted or are ineligible for standard therapeutic options; Arm B: Eligible participants must be considered unsuitable for intensive treatment with a curative intent (including stem cell transplantation), but eligible to receive Azacitidine (AZA) treatment with the following underlying diseases: AML (newly diagnosed or relapsed/refractory) according to the 2016 WHO classification only if Venetoclax (VEN) + hypomethylating agent (HMA) (or low-dose cytarabine) is not indicated or available; or high-risk or very high-risk MDS according to the 2016 WHO classification and IPSS-R; or CMML-2 according to the WHO 2016 criteria; Arm D: Very low, low, or intermediate-risk MDS according to the 2016 WHO classification and IPSS-R and the following: Transfusion dependence defined as requiring at least 3 red blood cell (RBC) units transfused within 16 weeks prior to C1D1; pre-transfusion hemoglobin (Hb) should be less than (<) 9.0 grams per decilitre (g/dL) to count towards the 3 units total, Relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment or endogenous serum erythropoietin (EPO) level greater than (>) 500 milliunits per milliliter (mU/mL). Exception: Del(5q) karyotype is allowed, provided prior treatment with lenalidomide has failed or participant was ineligible to receive lenalidomide
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
- Women of childbearing potential (WOCBP) must have a negative highly sensitive serum (beta-human chorionic gonadotropin) at screening and again within 48 hours prior to the first dose of study treatment. A urine or serum test is acceptable at subsequent time points
- A WOCBP must agree to all the following during the study and for 6 months after the last dose of study treatment: a) use a barrier method of contraception; b) use a highly effective preferably user-independent method of contraception; c) not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction; d) not plan to become pregnant; e) not breast-feeding
- A male must agree to all the following during the study and for 90 days after the last dose of study treatment: a) wear a condom when engaging in any activity that allows for passage of ejaculate to another person; b) not to donate sperm or freeze for future use for the purpose of reproduction; c) not plan to father a child. In addition, the participant should be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak
Exclusion Criteria:
- Acute promyelocytic leukemia according to World Health Organization 2016 criteria
- Known central nervous system involvement
- Prior treatment with a dihydroorotate dehydrogenase (DHODH) inhibitor for an oncology indication or intolerance to a DHODH inhibitor given for non-oncology indication
- Toxicities (except for alopecia, peripheral neuropathy, thrombocytopenia, neutropenia, anemia) from previous anticancer therapies that have not resolved to baseline or to Grade 1 or less
- Known allergies, hypersensitivity, or intolerance to JNJ-74856665, AZA, or VEN or the excipients of these treatments
Sites / Locations
- CHU de Nice Hopital de l Archet
- Hopital Saint-Louis
- Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
- Institut Universitaire du Cancer Toulouse Oncopole
- CHRU Tours Hôpital Bretonneau
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Samsung Medical Center
- The Catholic University of Korea Seoul St. Mary's Hospital
- Seoul National University Hospital
- Hosp. Univ. Vall D Hebron
- Hosp. Clinic I Provincial de Barcelona
- Inst. Cat. Doncologia-H Duran I Reynals
- Hosp. Univ. Fund. Jimenez Diaz
- Clinica Univ. de Navarra
- Hosp. Univ. Marques de Valdecilla
- Leicester Royal Infirmary
- University College London Hospitals
- Kings College Hospital
- The Christie Nhs Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Arm A: JNJ-74856665
Arm B: JNJ-74856665 + Azacitidine (AZA)
Arm C: JNJ-74856665 + Venetoclax (VEN)
Arm D: JNJ-74856665
Participants will receive JNJ-74856665 orally in a 21-day cycle. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until a recommended Phase 2 dose (RP2D) has been identified.
Participants will receive JNJ-74856665 orally in combination with AZA administered intravenously (IV) or subcutaneously (SC) in a 28-day cycle.
Participants will receive JNJ-74856665 orally in combination with VEN in a 28-day cycle.
Participants will receive JNJ-74856665 orally in a 21-day cycle. Participants with transfusion dependent relapsed/refractory Myelodysplastic Syndrome (MDS) will be included.