Brief Summary
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.
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.
Brief Title
A Study to Assess Adverse Events and Change in Disease Activity When Intravenous (IV) Pivekimab Sunirine is Given in Combination With Oral Venetoclax and IV or Subcutaneous Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML)
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
844-663-3742
Central Contact Email
abbvieclinicaltrials@abbvie.com
Completion Date
Completion Date Type
Estimated
Conditions
ACUTE MYELOID LEUKEMIA
Eligibility Criteria
Inclusion Criteria:
1. Participants must have newly diagnosed, untreated confirmed acute myeloid leukemia (AML) diagnosis as per the 5th edition of World Health Organization (WHO) criteria with a projected life expectancy of at least 12 weeks.
2. CD123-positive
3. Ineligible for intensive induction therapy (chemotherapy) defined by:
* ≥ 75 years of age OR
* ≥ 18 to 74 years of age with at least one of the following co-morbidities:
* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
* Cardiac history of congestive heart failure requiring treatment or ejection fraction ≤ 50% or chronic stable angina
* Diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%
* Creatinine clearance ≥ 30 mL/min to \< 45 mL/min
* Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × upper limit of normal (ULN)
* Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the medical monitor before study enrollment.
4. ECOG performance status 0 to 2 for subjects ≥ 75 years of age or 0 to 3 for subjects ≥ 18 to 74 years of age.
5. White blood cell (WBC) count \< 25 × 10\^9/L (hydroxyurea is permitted prior to beginning study treatment to reduce the WBC count to \< 25 × 10\^9/L).
6. Subjects must have adequate organ function:
* Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
* Adequate liver function as demonstrated by:
* Aspartate aminotransferase (AST) ≤ 3.0 × ULN\*,
* Alanine aminotransferase (ALT) ≤ 3.0 × ULN\*,
---\*Unless considered due to leukemic organ involvement
* Subjects \< 75 years of age may have total bilirubin ≤ 3 x ULN
* Subjects ≥ 75 years of age total bilirubin ≤ 1.5 × ULN unless elevated level is considered to be due to Gilbert's syndrome or hemolysis, total bilirubin must be \< 3 x ULN and direct bilirubin \< 1 x ULN
* Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × ULN International Normalized Ratio (INR) \<1.5
Exclusion Criteria:
* Acute promyelocytic leukemia (APL), blast phase of CML or AML with t(9;22) or BCR:ABL1 fusion, transformation from myeloproliferative neoplasm (MPN), Chronic Myelomonocytic Leukemia (CMML), myelodysplastic/myeloproliferative neoplasm unspecified, or myeloid sarcoma.
* Known active central nervous system (CNS) involvement with AML. Participants may have non-CNS extramedullary disease (excludes participants with myeloid sarcoma as the only disease manifestation at screening).
* Participants with history of any malignancies within 2 years prior to screening with exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of the breast, in situ - carcinomas of bladder and esophagus; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, and previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and have no evidence of relapse within 2 years.
* Participants must not have received a hypomethylating agent, any BCL-2 inhibitors including venetoclax, and/or chemotherapeutic agent for Myelodysplastic syndromes (MDS) or AML, CAR-T cell therapy, be currently participating in another clinical study, received any investigational treatment within 30 days prior to the first use of study combination product.
* Female participant must not be pregnant or breastfeeding and is not considering becoming pregnant or donating eggs during the study and for approximately 7 months after the last dose of any study drug. Female participant of childbearing potential must agree to use at least 1 protocol specified method of birth control and male participant, if sexually active with female partner(s) of childbearing potential, must agree to practice the protocol-specified contraception.
1. Participants must have newly diagnosed, untreated confirmed acute myeloid leukemia (AML) diagnosis as per the 5th edition of World Health Organization (WHO) criteria with a projected life expectancy of at least 12 weeks.
2. CD123-positive
3. Ineligible for intensive induction therapy (chemotherapy) defined by:
* ≥ 75 years of age OR
* ≥ 18 to 74 years of age with at least one of the following co-morbidities:
* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
* Cardiac history of congestive heart failure requiring treatment or ejection fraction ≤ 50% or chronic stable angina
* Diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%
* Creatinine clearance ≥ 30 mL/min to \< 45 mL/min
* Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × upper limit of normal (ULN)
* Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the medical monitor before study enrollment.
4. ECOG performance status 0 to 2 for subjects ≥ 75 years of age or 0 to 3 for subjects ≥ 18 to 74 years of age.
5. White blood cell (WBC) count \< 25 × 10\^9/L (hydroxyurea is permitted prior to beginning study treatment to reduce the WBC count to \< 25 × 10\^9/L).
6. Subjects must have adequate organ function:
* Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
* Adequate liver function as demonstrated by:
* Aspartate aminotransferase (AST) ≤ 3.0 × ULN\*,
* Alanine aminotransferase (ALT) ≤ 3.0 × ULN\*,
---\*Unless considered due to leukemic organ involvement
* Subjects \< 75 years of age may have total bilirubin ≤ 3 x ULN
* Subjects ≥ 75 years of age total bilirubin ≤ 1.5 × ULN unless elevated level is considered to be due to Gilbert's syndrome or hemolysis, total bilirubin must be \< 3 x ULN and direct bilirubin \< 1 x ULN
* Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × ULN International Normalized Ratio (INR) \<1.5
Exclusion Criteria:
* Acute promyelocytic leukemia (APL), blast phase of CML or AML with t(9;22) or BCR:ABL1 fusion, transformation from myeloproliferative neoplasm (MPN), Chronic Myelomonocytic Leukemia (CMML), myelodysplastic/myeloproliferative neoplasm unspecified, or myeloid sarcoma.
* Known active central nervous system (CNS) involvement with AML. Participants may have non-CNS extramedullary disease (excludes participants with myeloid sarcoma as the only disease manifestation at screening).
* Participants with history of any malignancies within 2 years prior to screening with exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of the breast, in situ - carcinomas of bladder and esophagus; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, and previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and have no evidence of relapse within 2 years.
* Participants must not have received a hypomethylating agent, any BCL-2 inhibitors including venetoclax, and/or chemotherapeutic agent for Myelodysplastic syndromes (MDS) or AML, CAR-T cell therapy, be currently participating in another clinical study, received any investigational treatment within 30 days prior to the first use of study combination product.
* Female participant must not be pregnant or breastfeeding and is not considering becoming pregnant or donating eggs during the study and for approximately 7 months after the last dose of any study drug. Female participant of childbearing potential must agree to use at least 1 protocol specified method of birth control and male participant, if sexually active with female partner(s) of childbearing potential, must agree to practice the protocol-specified contraception.
Inclusion Criteria
Inclusion Criteria:
1. Participants must have newly diagnosed, untreated confirmed acute myeloid leukemia (AML) diagnosis as per the 5th edition of World Health Organization (WHO) criteria with a projected life expectancy of at least 12 weeks.
2. CD123-positive
3. Ineligible for intensive induction therapy (chemotherapy) defined by:
* ≥ 75 years of age OR
* ≥ 18 to 74 years of age with at least one of the following co-morbidities:
* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
* Cardiac history of congestive heart failure requiring treatment or ejection fraction ≤ 50% or chronic stable angina
* Diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%
* Creatinine clearance ≥ 30 mL/min to \< 45 mL/min
* Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × upper limit of normal (ULN)
* Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the medical monitor before study enrollment.
4. ECOG performance status 0 to 2 for subjects ≥ 75 years of age or 0 to 3 for subjects ≥ 18 to 74 years of age.
5. White blood cell (WBC) count \< 25 × 10\^9/L (hydroxyurea is permitted prior to beginning study treatment to reduce the WBC count to \< 25 × 10\^9/L).
6. Subjects must have adequate organ function:
* Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
* Adequate liver function as demonstrated by:
* Aspartate aminotransferase (AST) ≤ 3.0 × ULN\*,
* Alanine aminotransferase (ALT) ≤ 3.0 × ULN\*,
---\*Unless considered due to leukemic organ involvement
* Subjects \< 75 years of age may have total bilirubin ≤ 3 x ULN
* Subjects ≥ 75 years of age total bilirubin ≤ 1.5 × ULN unless elevated level is considered to be due to Gilbert's syndrome or hemolysis, total bilirubin must be \< 3 x ULN and direct bilirubin \< 1 x ULN
* Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × ULN International Normalized Ratio (INR) \<1.5
1. Participants must have newly diagnosed, untreated confirmed acute myeloid leukemia (AML) diagnosis as per the 5th edition of World Health Organization (WHO) criteria with a projected life expectancy of at least 12 weeks.
2. CD123-positive
3. Ineligible for intensive induction therapy (chemotherapy) defined by:
* ≥ 75 years of age OR
* ≥ 18 to 74 years of age with at least one of the following co-morbidities:
* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
* Cardiac history of congestive heart failure requiring treatment or ejection fraction ≤ 50% or chronic stable angina
* Diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%
* Creatinine clearance ≥ 30 mL/min to \< 45 mL/min
* Moderate hepatic impairment with total bilirubin \> 1.5 to ≤ 3.0 × upper limit of normal (ULN)
* Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the medical monitor before study enrollment.
4. ECOG performance status 0 to 2 for subjects ≥ 75 years of age or 0 to 3 for subjects ≥ 18 to 74 years of age.
5. White blood cell (WBC) count \< 25 × 10\^9/L (hydroxyurea is permitted prior to beginning study treatment to reduce the WBC count to \< 25 × 10\^9/L).
6. Subjects must have adequate organ function:
* Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
* Adequate liver function as demonstrated by:
* Aspartate aminotransferase (AST) ≤ 3.0 × ULN\*,
* Alanine aminotransferase (ALT) ≤ 3.0 × ULN\*,
---\*Unless considered due to leukemic organ involvement
* Subjects \< 75 years of age may have total bilirubin ≤ 3 x ULN
* Subjects ≥ 75 years of age total bilirubin ≤ 1.5 × ULN unless elevated level is considered to be due to Gilbert's syndrome or hemolysis, total bilirubin must be \< 3 x ULN and direct bilirubin \< 1 x ULN
* Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × ULN International Normalized Ratio (INR) \<1.5
Gender
All
Gender Based
false
Keywords
Acute Myeloid Leukemia
Pivekimab Sunirine (PVEK)
Azacitidine
Venetoclax
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07581002
Org Class
Industry
Org Full Name
AbbVie
Org Study Id
M26-092
Overall Status
Not yet recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized Phase 2/3 Study Evaluating the Safety and Efficacy of Pivekimab Sunirine (PVEK) in Combination With Venetoclax and Azacitidine in Adult Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) Ineligible to Receive Intensive Chemotherapy
Primary Outcomes
Outcome Description
CR per modified 2022 European LeukemiaNet (ELN) response criteria in AML
Outcome Measure
Phase 2: Complete remission (CR)
Outcome Time Frame
Up to Approximately 71 Months
Outcome Description
CR per modified 2022 European LeukemiaNet (ELN) response criteria in AML
Outcome Measure
Phase 3: Complete remission (CR)
Outcome Time Frame
Up to Approximately 71 Months
Outcome Description
The time (in number of days) from randomization to death due to any cause.
Outcome Measure
Phase 3: Overall Survival (OS)
Outcome Time Frame
Up to Approximately 71 Months
Outcome Description
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.
Outcome Measure
Number of Participants with Adverse Events (AEs)
Outcome Time Frame
Up to approximately 71 months
Secondary Ids
Secondary Id
2025-523724-47-00
Secondary Outcomes
Outcome Description
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
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 2 and Phase 3: Composite Response
Outcome Description
Duration of CR (DoCR) defined as the time from achieving CR to hematologic relapse or death due to any cause, whichever occurs first.
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 2 and Phase 3: Duration of CR (DoCR)
Outcome Description
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).
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
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
Outcome Description
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.
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 3: Percentage of Participants with Transfusion Independence
Outcome Description
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.
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 3: Conversion from baseline transfusion dependence to post-baseline transfusion independence
Outcome Description
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).
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 3: Change from baseline in the EORCT QLQ-C30 physical functioning domains
Outcome Description
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).
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 3: Change from baseline in the remaining EORCT QLQ-C30 domains
Outcome Description
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).
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 3: Change from Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Utility Index and Visual Analog Scale (VAS) scores
Outcome Description
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.
Outcome Time Frame
Up to Approximately 71 Months
Outcome Measure
Phase 3: Change from Baseline to the responses to FACT GP5
Start Date
Start Date Type
Estimated
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Marina Konopleva
Investigator Email
marina.konopleva@einsteinmed.edu
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
MeSH Terms
LEUKEMIA, MYELOID, ACUTE
LEUKEMIA, MYELOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
VENETOCLAX
AZACITIDINE
AZA COMPOUNDS
ORGANIC CHEMICALS
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
RIBONUCLEOSIDES