Clinical trial NCT03030612: A Study of ARGX-110 in Combination With Azacytidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Lead sponsor: OncoVerity, Inc.
Sponsor class: INDUSTRY
Collaborators: name: argenx
name: Janssen Research & Development, LLC
First posted: 2017-01-25
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Number of Participants with Dose Limiting Toxicity (DLT)
timeFrame: Up to 3.6 years
measure: Phase 2: Overall Response Rate (ORR)
timeFrame: Up to 3.6 years
Secondary outcomes:
measure: Phase 1 and Phase 2: Number of Participants with Adverse Events
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Trough Concentration (Ctrough) of ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve from Time Zero to Infinite (AUC[0-infinity]) of ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCtau)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Apparent Volume of Distribution (Vd/F) of ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Total Systemic Clearance (CL) of ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Elimination Half-Life (t1/2) of ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Number of Participants with Minimal Residual Disease (MRD) to ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Number of Participants with Anti-drug Antibodies (ADA) to ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Number of Participants with Complete Remission (CR)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Number of Participants with CR with Incomplete Recovery (CRi)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Number of Participants with Morphologic Leukemia-free State (MLFS)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Number of Participants with Partial remission (PR)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Time to Response
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Duration of Response
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Relapse-Free Survival (RFS)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Overall Survival (OS)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Number of Participants with 30 Day and 60 Day Mortality
timeFrame: 30 and/or 60 days after the first administration
measure: Phase 1 and Phase 2: Number of Participants Achieving Transfusion Independence (TI)
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Time to Transfusion Independence
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Duration of Transfusion Independence
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Time to Neutrophil Recovery
timeFrame: Up to 3.6 years
measure: Phase 1 and Phase 2: Time to Platelet Recovery
timeFrame: Up to 3.6 years
measure: Biomarker Assessment of ARGX-110
timeFrame: Up to 3.6 years
measure: Phase 1: Levels of T, B and NK Cells
timeFrame: Up to 3.6 years
measure: Phase 1: Levels of B Cells
timeFrame: Up to 3.6 years
measure: Phase 1: Levels of NK Cells
timeFrame: Up to 3.6 years
Other outcomes:
Locations:
city: Marseille Cedex 9
country: France
city: Paris Cedex 10
country: France
city: Pierre - Bénite Cedex
country: France
city: Toulouse Cedex 9
country: France
city: Aarau
country: Switzerland
city: Bern
country: Switzerland
city: Zürich
country: Switzerland
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Riether C, Pabst T, Hopner S, Bacher U, Hinterbrandner M, Banz Y, Muller R, Manz MG, Gharib WH, Francisco D, Bruggmann R, van Rompaey L, Moshir M, Delahaye T, Gandini D, Erzeel E, Hultberg A, Fung S, de Haard H, Leupin N, Ochsenbein AF. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat Med. 2020 Sep;26(9):1459-1467. doi: 10.1038/s41591-020-0910-8. Epub 2020 Jun 29.