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History of Changes for Study: NCT04580121
A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420.
Latest version (submitted March 5, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 October 7, 2020 None (earliest Version on record)
2 November 3, 2020 Contacts/Locations and Study Status
3 December 3, 2020 Study Status
4 January 14, 2021 Contacts/Locations and Study Status
5 February 11, 2021 Contacts/Locations and Study Status
6 March 9, 2021 Study Status and Contacts/Locations
7 April 7, 2021 Study Status and Contacts/Locations
8 May 3, 2021 Study Status and Contacts/Locations
9 May 31, 2021 Oversight and Study Status
10 June 23, 2021 Arms and Interventions, Study Status, Eligibility and Study Description
11 July 23, 2021 Study Status and Contacts/Locations
12 August 19, 2021 Study Status and Contacts/Locations
13 September 16, 2021 Study Status
14 October 14, 2021 Study Status and Contacts/Locations
15 November 11, 2021 Contacts/Locations, Study Status, Arms and Interventions and Study Description
16 December 8, 2021 Study Status and Contacts/Locations
17 January 4, 2022 Study Status and Contacts/Locations
18 February 2, 2022 Study Status and Contacts/Locations
19 February 22, 2022 Contacts/Locations and Study Status
20 March 7, 2022 Study Status and Contacts/Locations
21 April 4, 2022 Contacts/Locations and Study Status
22 May 9, 2022 Study Status
23 May 18, 2022 Contacts/Locations and Study Status
24 June 8, 2022 Study Status
25 July 1, 2022 Study Status and Contacts/Locations
26 July 21, 2022 Contacts/Locations and Study Status
27 September 6, 2022 Outcome Measures, Arms and Interventions, Study Status, Study Design and Study Description
28 October 7, 2022 Study Status and Contacts/Locations
29 November 4, 2022 Study Status and Contacts/Locations
30 December 4, 2022 Study Status
31 January 2, 2023 Study Status
32 February 2, 2023 Study Status and Contacts/Locations
33 March 2, 2023 Study Status
34 April 6, 2023 Recruitment Status, Study Status and Contacts/Locations
35 July 24, 2023 Study Status and Contacts/Locations
36 August 18, 2023 Recruitment Status, Study Status and Contacts/Locations
37 September 15, 2023 Study Status and Contacts/Locations
38 October 12, 2023 Study Status and Contacts/Locations
39 November 9, 2023 Study Status and Contacts/Locations
40 December 11, 2023 Recruitment Status, Study Status, Contacts/Locations and Study Design
41 March 5, 2024 Study Status
Comparison Format:

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Changes (Merged) for Study: NCT04580121
March 2, 2023 (v33) -- April 6, 2023 (v34)

Changes in: Study Status and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: WP42004
Brief Title: A Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7283420.
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
Secondary IDs: 2020-000216-30 [EudraCT Number]
Open or close this module Study Status
Record Verification: March 2023 April 2023
Overall Status: Recruiting Suspended [The sponsor has put a temporary hold on recruitment until further notice.]
Study Start: November 4, 2020
Primary Completion: February 28, 2026 [Anticipated]
Study Completion: February 28, 2026 [Anticipated]
First Submitted: October 1, 2020
First Submitted that
Met QC Criteria:
October 7, 2020
First Posted: October 8, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
March 2 April 6, 2023
Last Update Posted: March 3 April 7, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief 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).
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).

Open or close this module Conditions
Conditions: Acute Myeloid Leukemia
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 220 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Part A: Single Participant Dose Escalation
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.
Drug: RO7283420
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.
Drug: Tocilizumab
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.
Other Names:
  • Actemra, RoActemra
Drug: Dasatinib
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.
Drug: Dexamethasone
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.
Drug: Paracetamol/acetaminophen
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.
Drug: Diphenhydramine
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.
Experimental: Part B: Multiple Participant Dose Escalation
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.
Drug: RO7283420
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.
Drug: Tocilizumab
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.
Other Names:
  • Actemra, RoActemra
Drug: Dasatinib
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.
Drug: Dexamethasone
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.
Drug: Paracetamol/acetaminophen
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.
Drug: Diphenhydramine
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.
Experimental: Part C: Dose Expansion
Participants will receive the respective RP2D for Group I and Group II.
Drug: RO7283420
RO7283420 at RP2D will be administered by IV infusion or SC injection as per dosing schedule determined in Part B.
Drug: Tocilizumab
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.
Other Names:
  • Actemra, RoActemra
Drug: Dasatinib
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.
Drug: Dexamethasone
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.
Drug: Paracetamol/acetaminophen
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.
Drug: Diphenhydramine
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percentage of Participants with Adverse Events (AEs)
[ Time Frame: From baseline up to 9 months ]

2. Percentage of Participants with Dose-Limiting Toxicities (DLTs)
[ Time Frame: From baseline up to 28 days ]

3. Recommended Phase II Dose (RP2D)
[ Time Frame: From baseline up to 7 months ]

Secondary Outcome Measures:
1. Maximum Reduction (%) from Baseline in Blast Count in Peripheral Blood and/or Bone Marrow (Group I Dose Escalation Cohorts only)
[ Time Frame: From baseline up to 7 months ]

2. Percentage of Participants who Achieve a Response
[ Time Frame: From baseline up to approximately 4 years ]

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).
3. Transfusion Independence
[ Time Frame: From baseline up to 7 months ]

4. Event-free Survival (EFS)
[ Time Frame: 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)
[ Time Frame: 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)
[ Time Frame: From baseline until the time of documented hematological relapse ]

7. Early Mortality Rate
[ Time Frame: From baseline to Day 30, and to Day 60 ]

8. Progression-free Survival (PFS)
[ Time Frame: 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
[ Time Frame: From baseline up to 7 months ]

10. Area Under the Curve (AUC) of RO7283420
[ Time Frame: 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
[ Time Frame: 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
[ Time Frame: 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
[ Time Frame: 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
[ Time Frame: 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
[ Time Frame: 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
[ Time Frame: 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 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: WP42004 https://forpatients.roche.com/
Telephone: 888-662-6728 (U.S. and Canada)
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: United States, California
City of Hope
[Recruiting]
Duarte, California, United States, 91010
UC Davis Comprehensive Cancer Center
[Recruiting]
Sacramento, California, United States, 95817
United States, Missouri
Washington University; Wash Uni. Sch. Of Med
[Withdrawn]
Saint Louis, Missouri, United States, 63110
United States, Texas
The University of Texas MD Anderson Cancer Center
[Recruiting]
Houston, Texas, United States, 77030-4009
Australia, Victoria
Peter MacCallum Cancer Centre; Medical Oncology
[Recruiting]
Melbourne, Victoria, Australia, 3000
The Alfred
[Recruiting]
Melbourne, Victoria, Australia, 3124
Canada, Ontario
Princess Margaret Cancer Center
[Recruiting]
Toronto, Ontario, Canada, M5G 1Z5
Denmark
Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
[Recruiting]
København Ø, Denmark, 2100
France
Institut Paoli Calmettes; Departement D' Onco-Hematologie
[Recruiting]
Marseille, France, 13273
Hopital De Haut Leveque; Hematologie Clinique
[Recruiting]
Pessac, France, 33604
Germany
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I
[Recruiting]
Dresden, Germany, 01307
Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III
[Recruiting]
München, Germany, 81377
Italy, Lombardia
ASST PAPA GIOVANNI XXIII; Ematologia
[Recruiting]
Bergamo, Lombardia, Italy, 24127
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
[Active, not recruiting]
Rozzano, Lombardia, Italy, 20089
Italy, Toscana
Ospedale Santa Chiara; Unita Operativa Di Ematologia
[Recruiting]
Pisa, Toscana, Italy, 56100
Spain
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
[Recruiting]
Barcelona, Spain, 08035
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
[Recruiting]
Barcelona, Spain, 08036
Hospital Univ. 12 de Octubre; Servicio de Hematologia
[Recruiting]
Madrid, Spain, 28041
Hospital Universitario la Fe; Servicio de Hematologia
[Recruiting]
Valencia, Spain, 46026
Spain, Barcelona
Institut Catala d?Oncologia Hospital Germans Trias i Pujol
[Recruiting]
Badalona, Barcelona, Spain, 08916
Taiwan
China Medical University Hospital; Oncology and Hematology
[Recruiting]
Taichung, Taiwan, 404
National Cheng Kung University Hospital; Oncology
[Recruiting]
Tainan, Taiwan, 00704
National Taiwan Universtiy Hospital; Division of Hematology
[Active, not recruiting]
Taipei, Taiwan, 100
United Kingdom
Churchill Hospital
[Recruiting]
Oxford, United Kingdom, OX3 7LJ
Royal Marsden NHS Foundation Trust
[Recruiting]
Sutton, United Kingdom, SM2 5PT
Open or close this module IPDSharing
Plan to Share IPD: 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).
Open or close this module References
Links:
Available IPD/Information:

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