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An Open-Label, Multi-Center, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420 as a Single Agent in Hematologic and Molecular Relapsed/Refractory Acute Myeloid Leukemia
This open-label, entry-into-human (EIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RO7283420. Escalating doses of RO7283420 will be administered to participants with Acute Myeloid Leukemia (AML) in order to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D).
The study will include AML participants with measurable disease, for whom standard-of-care (SOC) is not available. Two Groups of AML participants will be included in this study: * Group I participants will have hematologic relapse/refractory disease defined as participants not in complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). * Group II participants will have molecular relapse/persistent disease (participants with a CR or CRi, and a positive MRD based on local multi-parameter flow cytometry (MFC) or molecular assessment). The study consists of three parts: * Part A (single-participant dose escalation cohorts) - single participants from Group I will receive increment-based escalating doses until a Grade \>=2 AE related to RO7283420 or a clear pharmacodynamic effect * Part B (multiple-participant dose escalation cohorts) - multiple-participant cohorts of \>=3 participants will be enrolled for dose escalation for Group I and Group II independently. * Part C (dose expansion) - participants will receive the respective identified RP2D for that group. The treatment period for each participant will be up to 7 months with a maximum number of cycles depending on the dosing frequency the participant receives. 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. Additional 3, 5, or 9 cycles may be administered for the Q3W, Q2W, and QW dosing regimens, respectively, in case the participants have achieved at least partial remission (PR).
Age
18 - No limit years
Sex
ALL
Healthy Volunteers
No
UC Davis Comprehensive Cancer Center
Sacramento, California, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Peter MacCallum Cancer Centre; Medical Oncology
Melbourne, Victoria, Australia
The Alfred
Melbourne, Victoria, Australia
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
København Ø, Denmark
Institut Paoli Calmettes; Departement D' Onco-Hematologie
Marseille, France
Hopital De Haut Leveque; Hematologie Clinique
Pessac, France
Uniklinikum "Carl Gustav Carus"; Med. Klinik 1; Hämatologie, Zelltherapie und Medizinische Onkologie
Dresden, Germany
Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III
München, Germany
Start Date
November 4, 2020
Primary Completion Date
August 9, 2023
Completion Date
August 9, 2023
Last Updated
June 3, 2024
59
ACTUAL participants
RO7283420
DRUG
RO7283420
DRUG
Tocilizumab
DRUG
Dasatinib
DRUG
Dexamethasone
DRUG
Paracetamol/acetaminophen
DRUG
Diphenhydramine
DRUG
Lead Sponsor
Hoffmann-La Roche
NCT06285890
NCT06220162
NCT04065399
Data Source & Attribution
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