History of Changes for Study: NCT04580121

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

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	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:

Merged
Side-by-Side

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]

Study Status


Record Verification:	July 2022
Overall Status:	Recruiting
Study Start:	November 4, 2020
Primary Completion:	October 18, 2024 [Anticipated]
Study Completion:	October 18, 2024 [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:	July 1, 2022
Last Update Posted:	July 5, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Hoffmann-La Roche
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

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 (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) 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.

Each participant will receive up to 6 cycles of treatment with RO7283420. At the end of cycle 6, only participants achieving at least partial remission may receive three additional treatment cycles.

Conditions


Conditions:	Acute Myeloid Leukemia
Keywords:

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:	160 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: RO7283420 Part A 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 or subcutaneous (SC) injection Q3W at a starting dose of 0.15mg. 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: RO7283420 Part B 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 of RO7283420 once Q3W starting on C1D1 up to Cycle 6 to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). If needed, a step-up dosing regimen with more frequent administrations of RO7283420 during cycle 1 will be evaluated.	Drug: RO7283420 RO7283420 will be administered to participants by intravenous (IV) infusion or subcutaneous (SC) injection Q3W at a starting dose of 0.15mg. 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: RO7283420 Part C 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.

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 ]
Secondary Outcome Measures:
1.	Maximum Reduction (%) from Baseline in Blast Count in Peripheral Blood and/or Bone Marrow [ Time Frame: From baseline up to 7 months ]
2.	Percentage of Participants with >= 50% Reduction from Baseline in Blast Count in Peripheral Blood and/or Bone Marrow [ Time Frame: From baseline up to 7 months ]
3.	Number of MRD (Measurable Residual Disease) Negative Participants over time According to Local MRD Assessment [ Time Frame: From baseline up to 7 months ]
4.	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 of Cycle 2-9, at end of treatment visit (28 days after the last dose of RO7283420) ]
5.	Maximum Concentration (Cmax) of RO7283420 [ Time Frame: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1 of Cycle 2-9, at end of treatment visit (28 days after the last dose of RO7283420) ]
6.	Minimum Concentration (Cmin) of RO7283420 [ Time Frame: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1 of Cycle 2-9, at end of treatment visit (28 days after the last dose of RO7283420) ]
7.	Clearance (Cl) of RO7283420 [ Time Frame: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1 of Cycle 2-9, at end of treatment visit (28 days after the last dose of RO7283420) ]
8.	Volume (V) of RO7283420 [ Time Frame: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1 of Cycle 2-9, at end of treatment visit (28 days after the last dose of RO7283420) ]
9.	Half-life (T1/2) of RO7283420 [ Time Frame: Day 1, 2, 3, 8, 15 of Cycle 1 (each cycle is 21 days); Day 1 of Cycle 2-9, at end of treatment visit (28 days after the last dose of RO7283420) ]
10.	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, at end of treatment visit (28 days after the last dose of RO7283420) ]

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

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
	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 [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 [Recruiting] Taipei, Taiwan, 100
	United Kingdom
	Churchill Hospital [Recruiting] Oxford, United Kingdom, OX3 7LJ

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).

References


Links:
Available IPD/Information: