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Acute Myeloid LeukemiaPhase 1NCT04580121

A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420.

A Phase 1 study testing RO7283420, Tocilizumab and Dasatinib in people with Acute Myeloid Leukemia, run by Hoffmann-La Roche at 23 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
RO7283420, Tocilizumab and Dasatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
23 sitesin 10 countries
Study dates
4 Nov 2020to 9 Aug 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

23 sites in 10 countries.

23 sites in 10 countries

Spain5 sites

  • Institut Catala d?Oncologia Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitari Vall d'Hebron; Servicio de Hematologia

    Barcelona, 08035

  • Hospital Clínic i Provincial; Servicio de Hematología y Oncología

    Barcelona, 08036

  • Hospital Univ. 12 de Octubre; Servicio de Hematologia

    Madrid, 28041

  • Hospital Universitario la Fe; Servicio de Hematologia

    Valencia, 46026

Other trials in Spain

Italy3 sites

  • ASST PAPA GIOVANNI XXIII; Ematologia

    Bergamo, Lombardy, 24127

  • Ospedale Santa Chiara; Unita Operativa Di Ematologia

    Pisa, Tuscany, 56100

  • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia

    Rozzano, Lombardy, 20089

Other trials in Italy

Taiwan3 sites

  • China Medical University Hospital; Oncology and Hematology

    Taichung, 404

  • National Cheng Kung University Hospital; Oncology

    Tainan, 00704

  • National Taiwan Universtiy Hospital; Division of Hematology

    Taipei, 100

Other trials in Taiwan

United States2 sites

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

Australia2 sites

  • Peter MacCallum Cancer Centre; Medical Oncology

    Melbourne, Victoria, 3000

  • The Alfred

    Melbourne, Victoria, 3124

Other trials in Australia

France2 sites

  • Institut Paoli Calmettes; Departement D' Onco-Hematologie

    Marseille, 13273

  • Hopital De Haut Leveque; Hematologie Clinique

    Pessac, 33604

Other trials in France

Germany2 sites

  • Uniklinikum "Carl Gustav Carus"; Med. Klinik 1; Hämatologie, Zelltherapie und Medizinische Onkologie

    Dresden, 01307

  • Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III

    München, 81377

Other trials in Germany

United Kingdom2 sites

  • Churchill Hospital

    Oxford, OX3 7LJ

  • Royal Marsden NHS Foundation Trust

    Sutton, SM2 5PT

Other trials in United Kingdom

Canada1 site

  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

Denmark1 site

  • Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT

    København Ø, 2100

Other trials in Denmark

About this study

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

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).

Read the detailed description

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).

Being tested
RO7283420, Tocilizumab, Dasatinib, Dexamethasone, Paracetamol/acetaminophen
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RO7283420Drug

    RO7283420 will be administered to participants by intravenous (IV) infusion Q3W at a starting dose of 0.15mg. Starting dose levels (double step-up regimen, Q3W) for SC injections was the same as the highest dose levels that have been cleared in the IV double step-up cohorts at that timepoint. Each participant will receive up to 6, 9, and 18 cycles of treatment with RO7283420, when treated with Q3W, Q2W, or QW dosing regimens, respectively.

  • RO7283420Drug

    RO7283420 at RP2D will be administered by IV infusion or SC injection as per dosing schedule determined in Part B.

  • TocilizumabDrug

    Also called Actemra, RoActemra

    Tocilizumab will be administered as an IV infusion 8 mg/kg (for participants with a weight of 30 kg and above) and 12 mg/kg (for participants with a weight of less than 30 kg). Tocilizumab will be given as rescue medication.

  • DasatinibDrug

    Dasatinib 100 mg film-coated tablets will be administered daily until symptom resolution (up to 100 mg twice daily [BID] for a maximum 3 days); orally. Dasatinib will be given as rescue medication.

  • DexamethasoneDrug

    20 mg IV of dexamethasone will be administered as pre-medication at least 60 minutes prior to the all RO7283420 infusions or injections during cycle 1.

  • Paracetamol/acetaminophenDrug

    500 or 1000 mg of paracetamol/acetaminophen will be administered orally or by IV as pre-medication at least 30 minutes prior to each RO7283420 infusion or injection.

  • DiphenhydramineDrug

    25 mg or 50 mg of diphenhydramine will be administered orally or by IV as pre-medication at least 30 minutes prior to each RO7283420 infusion or injection.

Study groups in NCT04580121
Study groupRoleWhat they receive
Part A: Single Participant Dose EscalationExperimentalParticipants 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.
Receives: Drug: RO7283420; Drug: Tocilizumab; Drug: Dasatinib; Drug: Dexamethasone; Drug: Paracetamol/acetaminophen; Drug: Diphenhydramine
Part B: Multiple Participant Dose EscalationExperimentalMultiple-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.
Receives: Drug: RO7283420; Drug: Tocilizumab; Drug: Dasatinib; Drug: Dexamethasone; Drug: Paracetamol/acetaminophen; Drug: Diphenhydramine
Part C: Dose ExpansionExperimentalParticipants will receive the respective RP2D for Group I and Group II.
Receives: Drug: RO7283420; Drug: Tocilizumab; Drug: Dasatinib; Drug: Dexamethasone; Drug: Paracetamol/acetaminophen; Drug: Diphenhydramine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Adverse Events (AEs)

    Measured: From baseline up to 9 months

  2. Percentage of Participants with Dose-Limiting Toxicities (DLTs)

    Measured: From baseline up to 28 days

  3. Recommended Phase II Dose (RP2D)

    Measured: From baseline up to 7 months

Secondary outcomes (16)

  1. Maximum Reduction (%) from Baseline in Blast Count in Peripheral Blood and/or Bone Marrow (Group I Dose Escalation Cohorts only)

    Measured: From baseline up to 7 months

  2. Percentage of Participants who Achieve a Response

    Defined by ELN 2017 recommendations, i.e., complete remission (CR), complete remission with incomplete hematologic recovery (CRi), complete remission with absence of measurable residual disease (CRMRD-), and partial remission (PR).

    Measured: From baseline up to approximately 4 years

  3. Transfusion Independence

    Measured: From baseline up to 7 months

  4. Event-free Survival (EFS)

    Measured: From baseline to the time to progression, relapse, death from any cause, or start of a new treatment (up to approximately 4 years)

  5. Duration of Response (DoR)

    Measured: From first occurrence of a documented response until the time of documented relapse, disease progression or death from any cause, whichever occurs first (up to approximately 4 years)

  6. Time to Hematological Relapse (Group II Only)

    Measured: From baseline until the time of documented hematological relapse

  7. Early Mortality Rate

    Measured: From baseline to Day 30, and to Day 60

  8. Progression-free Survival (PFS)

    Measured: From Cycle 1 Day 1 to the first occurrence of documented disease progression, or death from any cause, whichever occurs first (up to approximately 4 years)

  9. Number of MRD (Measurable Residual Disease) Negative Participants over time According to Local MRD Assessment

    Measured: From baseline up to 7 months

  10. Area Under the Curve (AUC) of RO7283420

    Measured: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1, 2, 3, 8 of Cycle 2 only in case of triple step-up dosing; Day 1 of Cycle 2-9 (Q3W), 2-14 (Q2W), 2-27 (QW); end of treatment visit.

  11. Maximum Concentration (Cmax) of RO7283420

    Measured: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1, 2, 3, 8 of Cycle 2 only in case of triple step-up dosing; Day 1 of Cycle 2-9 (Q3W), 2-14 (Q2W), 2-27 (QW); end of treatment visit.

  12. Minimum Concentration (Cmin) of RO7283420

    Measured: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1, 2, 3, 8 of Cycle 2 only in case of triple step-up dosing; Day 1 of Cycle 2-9 (Q3W), 2-14 (Q2W), 2-27 (QW); end of treatment visit.

  13. Clearance (Cl) of RO7283420

    Measured: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1, 2, 3, 8 of Cycle 2 only in case of triple step-up dosing; Day 1 of Cycle 2-9 (Q3W), 2-14 (Q2W), 2-27 (QW); end of treatment visit.

  14. Volume (V) of RO7283420

    Measured: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1, 2, 3, 8 of Cycle 2 only in case of triple step-up dosing; Day 1 of Cycle 2-9 (Q3W), 2-14 (Q2W), 2-27 (QW); end of treatment visit.

  15. Half-life (T1/2) of RO7283420

    Measured: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1, 2, 3, 8 of Cycle 2 only in case of triple step-up dosing; Day 1 of Cycle 2-9 (Q3W), 2-14 (Q2W), 2-27 (QW); end of treatment visit.

  16. Incidence and Titer of Anti-drug Antibodies (ADA) against RO7283420

    Measured: Day 1, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1 and 8 of Cycle 2, Day 1 of Cycle 3-9 (Q3W), 3-14 (Q2W), 3-27 (QW); at end of treatment visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2020
  2. Study start4 Nov 2020
  3. Primary completion9 Aug 2023
  4. Study completion9 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04580121
Sponsor's protocol ID
WP42004
Other IDs
2020-000216-30
Status last verified
May 2024
First submitted
1 Oct 2020
Last updated
3 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Publications

  • Hutchings M, Korfi K, Montesinos P, Santoro A, Hou HA, Martinez-Sanchez P, Vives S, Galimberti S, Chen TY, Frigeni M, Garciaz S, Salamero Garcia O, Yeh SP, Yee K, Esteve J, Bajel A, Fleming S, Bretz AC, Attig J, Sun M, Nassiri S, Rutishauser T, Klein C, Ma YM, Schnetzler G, Vauleon S, Yu H, Barata T, Richard M, Simon S, Hinton H, Keshelava N, Subklewe M. Dose escalation study of the HLA-A2-WT1 CD3 bispecific antibody RO7283420 in relapsed/refractory acute myeloid leukemia. Blood Neoplasia. 2025 May 11;2(3):100110. doi: 10.1016/j.bneo.2025.100110. eCollection 2025 Aug.

    PubMed 40746940

  • Augsberger C, Hanel G, Xu W, Pulko V, Hanisch LJ, Augustin A, Challier J, Hunt K, Vick B, Rovatti PE, Krupka C, Rothe M, Schonle A, Sam J, Lezan E, Ducret A, Ortiz-Franyuti D, Walz AC, Benz J, Bujotzek A, Lichtenegger FS, Gassner C, Carpy A, Lyamichev V, Patel J, Konstandin N, Tunger A, Schmitz M, von Bergwelt-Baildon M, Spiekermann K, Vago L, Jeremias I, Marrer-Berger E, Umana P, Klein C, Subklewe M. Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC-specific T-cell bispecific antibody. Blood. 2021 Dec 23;138(25):2655-2669. doi: 10.1182/blood.2020010477.

    PubMed 34280257

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO7283420, Tocilizumab and Dasatinib in people with Acute Myeloid Leukemia, run by Hoffmann-La Roche at 23 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Spain, Italy, Taiwan, United States, Australia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Adverse Events (AEs) (time frame: From baseline up to 9 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04580121, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2024.

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