Acute Myeloid Leukemia MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Cusatuzumab
Product Code: JNJ-74494550
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CUSATUZUMAB
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each potential participant must satisfy all of the following criteria to be enrolled in the study: 1. =18 years of age 2. AML according to WHO 2016 criteria and fulfilling all of the following criteria that defines “not candidates for intensive chemotherapy”: ? =75 years of age or ? Comorbidity of at least one of the following: o Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 o Severe cardiac comorbidity defined as congestive heart failure or ejection fraction =50% o Severe pulmonary comorbidity defined as documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) =65% of expected, or forced expiratory volume in 1 second (FEV1) =65% of expected or dyspnea at rest requiring oxygen o Moderate hepatic impairment defined according to National Cancer Institute (NCI) organ dysfunction classification criteria (total bilirubin =1.5 up to 3 times upper lmit of normal [ULN]) o Creatinine clearance 30 mL/min (by MDRD formula) 5. A woman must be either: ? Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 12 months); ? Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies for at least 3 months: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that participant); true abstinence (when this is in line with the preferred and usual lifestyle of th
Exclusion criteria
Exclusion criteria: Any potential participant who meets any of the following criteria will be excluded from participating in the study: 1. Acute promyelocytic leukemia with t (15;17), or its molecular equivalent (PML-RARa). 2. Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system. 3. Use of immune suppressive agents for the past 4 weeks before the first administration of cusatuzumab on Cycle 1 Day 1. For regular use of systemic corticosteroids, participants may only be included if free of systemic corticosteroids for a minimum of 5 days before the first administration of cusatuzumab. 4. Prior treatment with a hypomethylating agent for treatment of AML or MDS 5. A diagnosis of other malignancy that requires concurrent non surgical treatment 6. Any active untreated systemic infection 7. A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening 8. Active systemic hepatitis infection requiring treatment or other clinically active liver disease 9. New York Heart Association Class IV heart failure or ongoing unstable angina 10. Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (ie, mannitol, an excipient of azacitidine). 11. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments. 12. Major surgery, (eg, requiring general anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Note: participants with planned surgical procedures to be conducted under local anesthesia may participate. In such cases, the investigator must notify the Sponsor before randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of cusatuzumab in combination with azacitidine in patients with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy; Secondary Objective: 1) To determine the below responses a) Complete response (CR) b) CR with incomplete recovery (CRi) c) CR with partial hematological revovery (CRh) d) CR without MRD (CRMRD-) e) Morphologic leukemia-free state (MLFS) f) Partial response (PR) g) Stable disease h) Relapse after CR, CRi, CRh i) Progressive Disease 2) To assess time to response and duration of response 3) To assess the safety profile of cusatuzumab in combination with azacitidine 4) To assess the pharmacokinetics of cusatuzumab alone and in combination with azacitidine 5) To assess the immunogenicity of cusatuzumab alone and in combination with azacitidine ;Primary end point(s): Complete response (CR) rate per ELN 2017 (Dohner 2017);Timepoint(s) of evaluation of this end point: Every 2 cycles (approximately every 2 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Rate of CRh 2. Rate of CR + CRh 3. Rate of CRi 4. Overall response rate (ORR) = Rate of CR+ CRh+ CRi 5. Rate of CR without MRD 6. Rate of MRD negativity among participants achieving CR, CRh, CRi, or MLFS ; defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3) 7. Time to response, defined as time from randomization to achieving the best response; duration of response, defined as time from achieving best response to disease relapse 8. Safety profile of Adverse Events (AE) and Serious Adverse Events (SAE) 9. Pharmacokinetics 10. Immunogenicity / anti-drug antibody testing ; Timepoint(s) of evaluation of this end point: 1 to 7. Every 2 cycles (approximately every 2 months) 8. Throughout the study 9. Cycle (C) 1 Day (D) 1, C1D3, C1D4, C1D7, C1D10, C1D17, Cycle =2 D3, Cycle =2 D17, C3D21 to C4D1, C5D21 to C6D1, and EOT (end of treatment) 10. C1D3, C1D17, Cycle =2 D3, and EOT | — |
Countries
Australia, Brazil, France, Israel, Italy, Russian Federation, Spain, Switzerland, Turkey, United States
Contacts
Public ContactGlobal Clinical Operations Spain
Janssen-Cilag, S.A.
Outcome results
None listed