A Study of ARGX-110 in Combination With Azacytidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS)

August 7, 2023 updated by: OncoVerity, Inc.

A Phase I/II, Open-label, Dose-Escalating Study With a Proof of Concept Cohort to Evaluate the Safety, Tolerability and Efficacy of ARGX-110 in Combination With Azacytidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS)

The purpose of this study is to determine the maximum tolerated dose (MTD) of ARGX-110 and/or the recommended Phase II dose (RP2D) in combination with a standard dose of azacytidine (AZA) in Phase 1; and to evaluate efficacy of ARGX-110 when administered at a RP2D level established in Phase I in combination with a standard dose of AZA (proof-of concept) by evaluating overall response rate (ORR) in Phase 2.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
38

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille Cedex 9, France
      • Paris Cedex 10, France
      • Pierre - Bénite Cedex, France
      • Toulouse Cedex 9, France
  • Switzerland
      • Aarau, Switzerland
      • Bern, Switzerland
      • Zürich, Switzerland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed informed consent form (ICF) indicating an understanding of the purposes, risks, and procedures required for the study and willingness and ability to participate in the study
  • Acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) (according to 2016 World Health Organization [WHO] classification definition of greater than or equal to [>=] 20 percent [%] blasts) (bone marrow) unsuitable for intensive treatment (including stem cell transplantation) with a curative intent, but eligible to receive azacytidine (AZA) treatment
  • Expected life expectancy >= 3 months, at the discretion of the investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Women of childbearing potential having a negative serum pregnancy test at screening and within 48 hours before infusion of ARGX-110 on Day -14, and willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) during the study and for at least 3 months after the last study drug administration

Exclusion Criteria:

  • Prior or concurrent malignancy, except for the following: (1) adequately treated basal cell or squamous cell skin cancer; (2) carcinoma in situ of the cervix; (3) carcinoma in situ of the breast; (4) incidental histological finding of Prostate cancer (Tumour, Node, Metastasis [TNM] stage T1a or T1b), or; (5) Any other cancer from which the subject has been disease-free for more than 2 years
  • Any previous AML or MDS chemo- or radiotherapy (with the exception of hydroxyurea/Litalir for leukocyte control which should be discontinued by the first day of AZA, local radiation therapy, therapy for basal or squamous cell carcinoma of the skin)
  • Treatment with any investigational product within 4 weeks before the first administration of ARGX-110
  • Any known active or chronic infection, including human immunodeficiency virus (HIV) and hepatitis B or C virus infection
  • Any other concurrent disease or medical condition that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ARGX-110 with Azacytidine (AZA)
Phase 1: Participants will receive loading dose of ARGX-110 1 milligram per kilogram (mg/kg) body weight (cohort 1), 3 mg/kg body weight (cohort 2), 10 mg/kg body weight (cohort 3) or 20 mg/kg body weight (cohort 4) administered intravenously (IV) in combination with AZA standard dose of 75 milligram per meter square (mg/m^2) body surface area (BSA) administered subcutaneously (SC) / intravenously (IV). Phase 2: Participants will receive loading dose of ARGX-110 IV at a recommended dose for Phase 2 (RP2D) level from phase 1 in combination with AZA standard dose of 75 mg/m^2 BSA, administered SC/IV as per local practice.
Drug: ARGX-110
ARGX-110 will be administered intravenously.
Other Names:
  • JNJ-74494550
  • Cusatuzumab
Drug: AZA
AZA will be administered subcutaneously/intravenously.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1: Number of Participants with Dose Limiting Toxicity (DLT)
Time Frame: Up to 3.6 years
DLTs will be defined as any of the following drug-related events: Any grade 3 or higher drug related non-hematological toxicity or; Grade 3 or higher IRRs or; inability to administer the next dose due to a drug-related adverse event or a delay of the administration of the next dose due to toxicities for more than 14 days despite adequate medication or; drug-related grade 4 febrile neutropenia or; drug-related grade 4 anemia which cannot be adequately treated.
Up to 3.6 years
Phase 2: Overall Response Rate (ORR)
Time Frame: Up to 3.6 years
ORR is defined as the sum of Complete remission (CR), CR with incomplete recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) at the ARGX-110 RP2D level that was established in Phase 1 according to established response criteria for Acute myeloid leukemia (AML).
Up to 3.6 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1 and Phase 2: Number of Participants with Adverse Events
Time Frame: Up to 3.6 years
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Up to 3.6 years
Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of ARGX-110
Time Frame: Up to 3.6 years
Cmax is the maximum observed concentration.
Up to 3.6 years
Phase 1 and Phase 2: Trough Concentration (Ctrough) of ARGX-110
Time Frame: Up to 3.6 years
Ctrough is defined as the observed serum concentration before dosing or at the end of the dosing interval.
Up to 3.6 years
Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve from Time Zero to Infinite (AUC[0-infinity]) of ARGX-110
Time Frame: Up to 3.6 years
AUC(0-infinity) is defined as area under the serum analyte concentration-time curve from time 0 to infinite time of ARGX-110.
Up to 3.6 years
Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCtau)
Time Frame: Up to 3.6 years
AUCtau is the area under the serum concentration-time curve during the dosing interval.
Up to 3.6 years
Phase 1 and Phase 2: Apparent Volume of Distribution (Vd/F) of ARGX-110
Time Frame: Up to 3.6 years
Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
Up to 3.6 years
Phase 1 and Phase 2: Total Systemic Clearance (CL) of ARGX-110
Time Frame: Up to 3.6 years
CL is the total systemic clearance of drug after intravenous (IV) administration.
Up to 3.6 years
Phase 1 and Phase 2: Elimination Half-Life (t1/2) of ARGX-110
Time Frame: Up to 3.6 years
t1/2 is defined as the time measured for the serum concentration to decrease by 1 half of its original concentration.
Up to 3.6 years
Phase 1 and Phase 2: Number of Participants with Minimal Residual Disease (MRD) to ARGX-110
Time Frame: Up to 3.6 years
Minimal residual disease assessments will be performed on bone marrow aspirates and/or whole blood by flow cytometry.
Up to 3.6 years
Phase 1 and Phase 2: Number of Participants with Anti-drug Antibodies (ADA) to ARGX-110
Time Frame: Up to 3.6 years
Venous blood samples and bone marrow aspirate will be used to evaluate presence of anti-drug antibodies to ARGX-110. Participants with titer of confirmed positive samples for ARGX-110 antibodies will be reported.
Up to 3.6 years
Phase 1 and Phase 2: Number of Participants with Complete Remission (CR)
Time Frame: Up to 3.6 years
Complete remission is defined as number of participants who have bone marrow blasts less than (<) 5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>) 1.0 * 10^9 per liter (L) (1000 per microliter [µL]); platelet count > 100 * 10^9/L (100.000/mc); independence of red cell transfusions.
Up to 3.6 years
Phase 1 and Phase 2: Number of Participants with CR with Incomplete Recovery (CRi)
Time Frame: Up to 3.6 years
CRi is defined as number of participants who have all CR criteria except for residual neutropenia (< 1.0 * 10^9/L [1000/mc]) or thrombocytopenia (< 100 * 10^9/L [100.000/mc]).
Up to 3.6 years
Phase 1 and Phase 2: Number of Participants with Morphologic Leukemia-free State (MLFS)
Time Frame: Up to 3.6 years
MLFS is defined as number of participants who have bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required.
Up to 3.6 years
Phase 1 and Phase 2: Number of Participants with Partial remission (PR)
Time Frame: Up to 3.6 years
PR is defined as number of participants who have all hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
Up to 3.6 years
Phase 1 and Phase 2: Time to Response
Time Frame: Up to 3.6 years
Time to response is defined as response measured from the time from first dose of study drug to date of response (CR, CRi, MLFS, PR).
Up to 3.6 years
Phase 1 and Phase 2: Duration of Response
Time Frame: Up to 3.6 years
Duration of response is defined as the date of achievement of a response (CR, CRi, MLFS, PR) until the date of relapse.
Up to 3.6 years
Phase 1 and Phase 2: Relapse-Free Survival (RFS)
Time Frame: Up to 3.6 years
RFS is defined as disease relapse or participant death from any cause; measured from the date of achievement of a remission (CR, CRi) until the date of relapse or death from any cause.
Up to 3.6 years
Phase 1 and Phase 2: Overall Survival (OS)
Time Frame: Up to 3.6 years
OS is defined as death from any cause; measured from the date of first dose to the date of death from any cause.
Up to 3.6 years
Phase 1 and Phase 2: Number of Participants with 30 Day and 60 Day Mortality
Time Frame: 30 and/or 60 days after the first administration
Number of participants with 30 Day and 60 Day Mortality will be reported.
30 and/or 60 days after the first administration
Phase 1 and Phase 2: Number of Participants Achieving Transfusion Independence (TI)
Time Frame: Up to 3.6 years
Number of participants reaching greater than or equal to (>=) 8 consecutive weeks without red blood cell (RBC-TI) and/or platelet (PLT-TI) transfusion. The first day of the >=8-week period with no transfusions is noted as the time at which participants first achieved TI.
Up to 3.6 years
Phase 1 and Phase 2: Time to Transfusion Independence
Time Frame: Up to 3.6 years
Time until TI for RBC and/or PLT will be measured from the date of entry into a study to the first day of the 8-weeks period with no transfusions.
Up to 3.6 years
Phase 1 and Phase 2: Duration of Transfusion Independence
Time Frame: Up to 3.6 years
Time between the last transfusion before the start of the TI period and the first transfusion after the start of the TI period, which occurred >=8 weeks later.
Up to 3.6 years
Phase 1 and Phase 2: Time to Neutrophil Recovery
Time Frame: Up to 3.6 years
Time to neutrophil recovery will be calculated from number of days from Day 1 of commencing study treatment to first day neutrophils 0.5 * 10^9 per liter or 1.0 * 10^9 per liter.
Up to 3.6 years
Phase 1 and Phase 2: Time to Platelet Recovery
Time Frame: Up to 3.6 years
Time to platelet recovery will be calculated from number of days from day 1 of commencing study treatment to first day neutrophils 50 * 10^9 per liter or 100 * 10^9 per liter.
Up to 3.6 years
Biomarker Assessment of ARGX-110
Time Frame: Up to 3.6 years
Biomarkers including CD70 and CD27 assessment will be performed on bone marrow aspirates and/or whole blood.
Up to 3.6 years
Phase 1: Levels of T, B and NK Cells
Time Frame: Up to 3.6 years
Levels of T, B and NK cells will be reported by immunophenotyping (performed by flow cytometry or mass cytometry). .
Up to 3.6 years
Phase 1: Levels of B Cells
Time Frame: Up to 3.6 years
Levels of B cells will be reported.
Up to 3.6 years
Phase 1: Levels of NK Cells
Time Frame: Up to 3.6 years
Levels of NK cells will be reported.
Up to 3.6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
OncoVerity, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Janssen Research & Development, LLC
argenx

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 23, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR108756
  • 2016-002151-17 (EudraCT Number)
  • ARGX-110-1601 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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