CUSATUZUMAB for Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Men and women ≥18 years old."}
• {"criterion_text":"- Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study."}
• {"criterion_text":"- Diagnosis of AML according to ICC 2022 (with the exclusion of MDS/AML with 10-19% blasts)."}
• {"criterion_text":"- Previously untreated AML except may have received emergency leukapheresis, hydroxyurea, before study entry to control hyperleukocytosis."}
• {"criterion_text":"- Deemed unfit for intensive chemotherapy by meeting the criterial listed in the Protocol"}
• {"criterion_text":"- Adequate liver and renal function, as per defined in the Protocol"}
• {"criterion_text":"- Women of childbearing potential (WOCBP), defined as fertile women between menarche and post menopause unless permanently sterile, must have a negative highly sensitive serum β-human chorionic gonadotropin (β-hCG) or urine pregnancy test at screening"}
• {"criterion_text":"- Must be willing to use contraception as consistent with institutional guidelines regarding the use of contraceptive methods for participants participating in clinical studies"}
• {"criterion_text":"- Participants with HIV infection are eligible for the trial if the criteria included in the Protocol are met"}

Exclusion criteria

• {"criterion_text":"- Any prior treatment for AML (except those outlined in Inclusion Criterion #4)"}
• {"criterion_text":"- History of prior HSCT (allogeneic or autologous transplants)."}
• {"criterion_text":"- Active hepatitis B or C infection or other clinically active liver diseases as defined in the Protocol"}
• {"criterion_text":"- Congestive heart failure severity that is New York Heart Association Class III or IV"}
• {"criterion_text":"- Unstable angina"}
• {"criterion_text":"- Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, or azacitidine or their excipients (e.g., mannitol, an excipient of azacitidine)"}
• {"criterion_text":"- Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function"}
• {"criterion_text":"- Any condition for which, in the investigator’s opinion, participation would not be in the best interest of the participant (e.g., compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments"}
• {"criterion_text":"- Major surgery (e.g., requiring general anesthesia) ≤4 weeks prior to initiation of study treatment"}
• {"criterion_text":"- Participant has received a HMA or venetoclax for MDS or myeloproliferative neoplasm"}
• {"criterion_text":"- Leukemic involvement in the central nervous system"}
• {"criterion_text":"- Participants with acute promyelocytic leukemia (APL)"}
• {"criterion_text":"- ECOG performance status of 4 for participants 18 to 74 years of age and ECOG performance status of 3 or 4 for participants ≥75 years of age"}
• {"criterion_text":"- Use of immune suppressive agents ≤4 weeks before the first administration of cusatuzumab. Participants may be included if free of systemic corticosteroids >5 days before the first administration of cusatuzumab with the exception of corticosteroids at physiologic replacement doses"}
• {"criterion_text":"- Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug"}
• {"criterion_text":"- Active malignancies (i.e., progressing or requiring treatment change in the last 24 months), including advanced malignant hepatic tumors, other than the disease being treated under study. Exceptions listed in the protocol."}
• {"criterion_text":"- Any active systemic infection"}

Primary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Complete remission (CR) rate defined as rate of complete remission per European Leukemia Network (ELN) 2022","definition_or_measurement_approach":"Rate of complete remission per ELN 2022"}
• {"endpoint_text":"- Event-free survival (EFS) per ELN 2022","definition_or_measurement_approach":"Per ELN 2022 definitions"}
• {"endpoint_text":"- Composite CR (CRc) rate = the sum of rates for CR+CRh+CRi (CRh and CRi is defined as CR with partial hematologic recovery and incomplete hematologic recovery respectively) per ELN 2022","definition_or_measurement_approach":"CRc = CR + CRh + CRi per ELN 2022"}
• {"endpoint_text":"- Rates of CRh, CRi, and MLFS","definition_or_measurement_approach":"Per ELN 2022 definitions"}
• {"endpoint_text":"- Duration of complete remission defined as the time from first CR to hematological relapse or death from any cause","definition_or_measurement_approach":"Time from first documented CR to hematological relapse or death"}
• {"endpoint_text":"- Time to first complete remission defined as time from randomization to first occurrence of CR","definition_or_measurement_approach":"Time from randomization to first documented CR"}
• {"endpoint_text":"- Rate of measurable residual disease (MRD) negativity in participants achieving CR, CRh or CRi per ELN 2022 guidelines for MRD testing","definition_or_measurement_approach":"MRD negativity rate assessed per ELN 2022 MRD testing guidelines"}
• {"endpoint_text":"- Proportion of participants proceeding to hematopoietic stem cell transplantation (HSCT)","definition_or_measurement_approach":"Proportion of participants who undergo HSCT"}
• {"endpoint_text":"- OS in participants undergoing HSCT","definition_or_measurement_approach":"Overall survival measured in subset undergoing HSCT"}
• {"endpoint_text":"- Adverse events (AEs) per NCI CTCAE criteria","definition_or_measurement_approach":"AEs graded and reported per NCI CTCAE criteria"}
• {"endpoint_text":"- Serious AEs (SAEs) and AEs leading to study drug discontinuation","definition_or_measurement_approach":"Incidence and details of SAEs and AEs causing discontinuation"}
• {"endpoint_text":"- Incidence of dose modifications (interruptions/delays) due to AEs","definition_or_measurement_approach":"Incidence of dose interruptions or delays attributable to AEs"}
• {"endpoint_text":"- Clinical laboratory tests, ECGs, physical examination findings, and vital signs","definition_or_measurement_approach":"Routine clinical safety assessments (labs, ECGs, physical exam, vitals)"}
• {"endpoint_text":"- Serum concentration-time data and pharmacokinetic parameters as feasible for cusatuzumab","definition_or_measurement_approach":"PK sampling to derive serum concentration-time profiles and PK parameters for cusatuzumab"}
• {"endpoint_text":"- Incidence of anti-cusatuzumab antibodies","definition_or_measurement_approach":"Immunogenicity assessment for anti-cusatuzumab antibodies"}
• {"endpoint_text":"- Incidence of neutralizing antibodies (NAb)","definition_or_measurement_approach":"Assessment for neutralizing antibodies"}
• {"endpoint_text":"- OS and CR as well as other endpoints","definition_or_measurement_approach":"OS and CR measurements as defined in primary and other endpoints"}
• {"endpoint_text":"- Rate of conversion from MRD negativity to MRD positivity in participants achieving CR, CRh or CRi","definition_or_measurement_approach":"Rate of conversion from MRD negative to MRD positive status among those achieving CR/CRh/CRi"}

Germany

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

04-12-2025

Processing Time Days

518

Number Of Sites

3

Number Of Participants

20

Spain

Earliest CTIS Part Ii Submission Date

24-07-2025

Latest Decision Or Authorization Date

04-12-2025

Processing Time Days

133

Number Of Sites

6

Number Of Participants

9

Primary sponsor

Full Name

Oncoverity Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

codes: 1,10,11,12,13,14,2,3,4,5,6,8

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"codes: 1,10,11,12,13,14,2,3,4,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Smithers","duties_or_roles":"codes: 4","organisation_type":"Health care"}
• {"country":"United States","full_name":"Hematologics","duties_or_roles":"codes: 4","organisation_type":"Health care"}
• {"country":"United States","full_name":"Neogenomics Inc.","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Aml Jv LLC","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}