Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UC Davis
Dates
study started
estimated completion

Description

Summary

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).

Official Title

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

Details

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 (participants not in CR or CRi i.e. with >=5% blast cells in the bone marrow (BM) or presence of circulating blast) - 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) 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. Each participant will receive up to 6 cycles of treatment with RO7283420. At the end of Cycle 6, at the discretion of the Investigator (based on the assessment of clinical benefit), the participant could receive up to 3 additional treatment cycles.

Keywords

Acute Myeloid Leukemia Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Dasatinib Tocilizumab

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 and Group II) will be included.
  • Participants who have received hematopoietic stem cell transplant (HSCT) must have the HSCT performed ≥ 28 days prior to screening, having demonstrated hematological engraftment and do not have an active Graft versus Host disease
  • 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 and 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

You CAN'T join if...

  • 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)
  • Glomerular proteinuria (Grade >= 2) with presence of transferrin and/or IgG in the urine
  • Another primary malignancy (other than AML) that requires active therapy. Adjuvant hormonal therapy is allowed
  • History of autoimmune disease
  • Clinical evidence or history of central nervous system (CNS) leukemia
  • Presence of isolated 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

Locations

  • UC Davis Comprehensive Cancer Center not yet accepting patients
    Sacramento California 95817 United States
  • City of Hope not yet accepting patients
    Duarte California 91010 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Hoffmann-La Roche
ID
NCT04580121
Phase
Phase 1
Study Type
Interventional
Last Updated