A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420.
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- With confirmed diagnosis of primary or secondary AML according to WHO classification 2016, with measurable disease. Eligible participants need to have received standard-of-care (SOC) and have no other SOC options available Participants who are not willing to receive SOC will be not eligible. Two groups of participants (Group I - hematologic relapsed/refractory and Group II - molecular relapsed/refractory) will be included
- Participants who have received hematopoietic stem cell transplant (HSCT) must have the HSCT performed ≥ 90 days prior to the first dose of RO7283420 on Cycle 1 Day 1, having demonstrated hematological engraftment and do not have an active Graft versus Host Disease, not requiring immunosuppressive treatment (including but not limited to cyclosporine, tacrolimus, sirolimus, and mycophenolate), which must be stopped at least 28 days prior to the first dose of RO7283420 on Cycle 1 Day 1
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Peripheral blast counts =< 20,000/mm3 on Cycle 1 Day 1 prior to the first dosing
- Confirmed genotype of HLA-A*02
- Adequate renal (a creatinine clearance of >=50 mL/min as calculated according to the Cockroft-Gault formula) and adequate liver test results
- Male or female participants agree to use contraception and the abstinence requirements to prevent exposure of an embryo to the study treatment
Exclusion Criteria:
- Acute promyelocytic leukemia (APL)
- Core Binding Factor (CBF)-AML Note: participants with r/r CBF-AML after at least 2 salvage attempts can be enrolled into the study
- Group II only: participants with normal karyotype and a favorable molecular profile according to ELN guideline 2017
- Participants with active bacterial, fungal or viral infection considered by the Investigator to be clinically uncontrolled or of unacceptable risk upon the induction of neutropenia (i.e. participants who are or should be on antimicrobial agents for the treatment of active infection)
- Grade >= 2 glomerular proteinuria at screening or on Cycle 1 Day 1 prior to the first dosing.
- Another primary malignancy (other than AML) that requires active therapy. Adjuvant hormonal therapy is allowed
- Clinical evidence or history of central nervous system (CNS) leukemia
- Presence of extramedullary disease at screening
- Current or past history of CNS disease, such as stroke, CNS inflammation, epilepsy, CNS vasculitis, or neurodegenerative disease
- Participants who have a history of clinically significant liver disease, including liver cirrhosis (e.g. Child-Pugh class B and C) or participants who have a history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection
- Participants who might refuse to receive blood products and/or have known hypersensitivity to any of the components of RO7283420, tocilizumab, or dasatinib
Sites / Locations
- City of Hope
- UC Davis Comprehensive Cancer Center
- Washington University; Wash Uni. Sch. Of Med
- The University of Texas MD Anderson Cancer Center
- Peter MacCallum Cancer Centre; Medical Oncology
- The Alfred
- Princess Margaret Cancer Center
- Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KATRecruiting
- Institut Paoli Calmettes; Departement D' Onco-HematologieRecruiting
- Hopital De Haut Leveque; Hematologie Clinique
- Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I
- Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik IIIRecruiting
- ASST PAPA GIOVANNI XXIII; Ematologia
- Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
- Ospedale Santa Chiara; Unita Operativa Di Ematologia
- Institut Catala d?Oncologia Hospital Germans Trias i Pujol
- Hospital Universitari Vall d'Hebron; Servicio de Hematologia
- Hospital Clínic i Provincial; Servicio de Hematología y Oncología
- Hospital Univ. 12 de Octubre; Servicio de Hematologia
- Hospital Universitario la Fe; Servicio de Hematologia
- China Medical University Hospital; Oncology and HematologyRecruiting
- National Cheng Kung University Hospital; OncologyRecruiting
- National Taiwan Universtiy Hospital; Division of Hematology
- Churchill HospitalRecruiting
- Royal Marsden NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Part A: Single Participant Dose Escalation
Part B: Multiple Participant Dose Escalation
Part C: Dose Expansion
Participants from Group I will receive escalating doses of RO7283420, once every 3 weeks (Q3W) starting on Cycle 1, Day 1 (C1D1) for up to 6 cycles with a starting dose of 0.15mg.
Multiple-participant cohorts of >= 3 participants will be enrolled for dose escalation for Group I and Group II independently. Participants will be administered a starting dose of 0.15 mg or highest dose administered in Part A. Each participant will receive up to 6, 9, and 18 cycles of treatment with RO7283420, when treated with Q3W, every-2-weeks (Q2W), or once-a-week (QW) dosing regimens, respectively to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Additionally, step-up dosing regimens with more frequent administrations of RO7283420 during cycle 1 will be evaluated.
Participants will receive the respective RP2D for Group I and Group II.