Cancer is a condition where cells in a specific part of the body grow and reproduce uncontrollably. Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow (the spongy tissue inside the bones) that affects white blood cells that helps to fight infections and also prevents normal blood cell production. This study will assess the adverse events and changes in the disease activity when Pivekimab Sunirine (PVEK) is given in combination with Venetoclax (VEN) and Azacitidene (AZA) in adult participants with AML ineligible to receive intensive chemotherapy. Pivekimab sunirine is a drug being evaluated in the treatment of AML.This is a Phase 2/Phase 3, study of PVEK. Phase 2 is open-label and randomized. Phase 3 is double-blind, randomized. Phase 2 and Phase 3 studies test potential new treatments in patients with a condition or disease. Open-label means that both patients and study doctors know which study treatment is given to patients in Phase 2 of the study. Double-blind means that neither the patients nor the study doctors know who is given which study treatment in Phase 3 of the study. Approximately 660 adult participants will be enrolled in 180 sites worldwide. In Phase 2 of the study, patients will be randomized to receive PVEK + VEN + AZA or standard of care treatment with VEN + AZA. In Phase 3, patients will be randomized to receive PVEK + VEN + AZA or a matching-placebo for PVEK plus VEN + AZA. PVEK is given as an infusion into the vein, AZA is given as an injection under your skin (subcutaneous) or as an infusion into the vein (intravenous) (depending on country where patient enrolls), and VEN is a tablet given by mouth. The total study duration is approximately 71 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
660
City of Hope National Medical Center /ID# 279568
Duarte, California, United States
RECRUITINGMoffitt Cancer Center /ID# 279192
Tampa, Florida, United States
RECRUITINGWinship Cancer Institute of Emory University /ID# 279006
Atlanta, Georgia, United States
RECRUITINGWashington University /ID# 280295
St Louis, Missouri, United States
Phase 2: Complete remission (CR)
CR per modified 2022 European LeukemiaNet (ELN) response criteria in AML
Time frame: Up to Approximately 71 Months
Phase 3: Complete remission (CR)
CR per modified 2022 European LeukemiaNet (ELN) response criteria in AML
Time frame: Up to Approximately 71 Months
Phase 3: Overall Survival (OS)
The time (in number of days) from randomization to death due to any cause.
Time frame: Up to Approximately 71 Months
Number of Participants with Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Time frame: Up to approximately 71 months
Phase 2 and Phase 3: Composite Response
Composite Complete Remission (CR) + Complete Remission with Incomplete Blood Count Recovery (CRi) and Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh) response defined as participants achieving CR plus CRi, and CR plus CRh
Time frame: Up to Approximately 71 Months
Phase 2 and Phase 3: Duration of CR (DoCR)
Duration of CR (DoCR) defined as the time from achieving CR to hematologic relapse or death due to any cause, whichever occurs first.
Time frame: Up to Approximately 71 Months
Phase 2: Change from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORCT QLQ-C30) domains
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales, 3 symptom scales, a global health status/Quality of Life (QoL) scale, and 6 single items. Participants rate items on a 4-point scale ranging from 1 (not at all) to 4 (very much).
Time frame: Up to Approximately 71 Months
Phase 3: Percentage of Participants with Transfusion Independence
Transfusion independence is defined as a period of at least 56 days with no red blood cell (RBC) and no platelet transfusion during the treatment period.
Time frame: Up to Approximately 71 Months
Phase 3: Conversion from baseline transfusion dependence to post-baseline transfusion independence
Conversion from baseline transfusion dependence to post-baseline transfusion independence is defined as a period of at least 56 days with no RBC and no platelet transfusion during the treatment period among participants who were transfusion dependent within at least 28 days prior to study treatment.
Time frame: Up to Approximately 71 Months
Phase 3: Change from baseline in the EORCT QLQ-C30 physical functioning domains
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Participants rate items on a 4-point scale ranging from 1 (not at all) to 4 (very much).
Time frame: Up to Approximately 71 Months
Phase 3: Change from baseline in the remaining EORCT QLQ-C30 domains
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Participants rate items on a 4-point scale ranging from 1 (not at all) to 4 (very much).
Time frame: Up to Approximately 71 Months
Phase 3: Change from Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Utility Index and Visual Analog Scale (VAS) scores
The EQ-5D-5L is a generic preference instrument that has been validated in numerous cancer populations. The EQ-5D-5L consists of 2 components: the descriptive system and the visual analog scale (VAS). The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems).
Time frame: Up to Approximately 71 Months
Phase 3: Change from Baseline to the responses to FACT GP5
Functional Assessment of Cancer Therapy - General item GP5 (FACT GP5) item is a one-item questionnaire that is used to assess overall treatment tolerability in participants by assessing the overall side effect impact on participants. This item is rated on a 5-point Likert scale from 0 = "not at all" to 4 = "very much" using a 7-day recall period.
Time frame: Up to Approximately 71 Months
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Montefiore Medical Center - Moses Campus /ID# 279399
The Bronx, New York, United States
RECRUITINGThe University of Texas MD Anderson Cancer Center /ID# 279402
Houston, Texas, United States
RECRUITINGUniversitaetsklinikum St. Poelten /ID# 278835
Sankt Pölten, Lower Austria, Austria
RECRUITINGHanusch-Krankenhaus /ID# 279467
Vienna, State of Vienna, Austria
RECRUITINGMedizinische Universitaet Graz /ID# 278830
Graz, Styria, Austria
RECRUITINGOrdensklinikum Linz Elisabethinen /ID# 278824
Linz, Upper Austria, Austria
RECRUITING...and 25 more locations