RecruitingPhase 2 / Phase 3

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)

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Infusions, Injections, Pills, Blood draws

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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 effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether adding pivekimab sunirine to venetoclax and azacitidine helps treat acute myeloid leukemia (AML), a cancer of the blood and bone marrow. It also checks side effects. It is for adults with newly diagnosed, untreated AML who cannot receive intensive chemotherapy.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have confirmed, newly diagnosed AML that has not been treated, and be expected to live at least 12 weeks.
  • Have leukemia cells that test positive for CD123, a marker on cells.
  • Be age 75 or older, or age 18–74 with health problems that make intensive chemotherapy unsuitable. These may include limits on daily activity or heart, lung, kidney, or liver problems. Other health problems need study approval.
  • Meet the study's limits for daily activity: an ECOG score of 0–2 if age 75 or older, or 0–3 if age 18–74. This score measures how well you can do daily tasks.
  • Have a white blood cell count below 25 billion per liter. Hydroxyurea may be used before study treatment to lower this count.
  • Have kidney, liver, and blood-clotting test results within the study's required limits. Some liver test limits depend on your age and other health conditions.

Who can't join

  • Have certain other blood cancers or AML types, including APL, advanced CML, AML with certain gene changes, or AML that developed from certain blood disorders. Myeloid sarcoma, a tumor made of leukemia cells, is also listed as an exclusion.
  • Have active AML in the brain or spinal cord.
  • Have had another cancer within the past 2 years. Exceptions include certain treated early-stage or skin cancers, and cancers treated to cure them with no return within 2 years.
  • Have received certain drugs for MDS, a bone marrow disorder, or AML. These include hypomethylating drugs, BCL-2 blockers such as venetoclax, or chemotherapy.
  • Have received CAR-T cell therapy, a treatment using changed immune cells.
  • Be taking part in another clinical study, or have received an experimental treatment within 30 days before starting study treatment.
  • Be pregnant, breastfeeding, or planning pregnancy or egg donation during the study or for about 7 months after the last study drug dose.
  • Be unable to follow the study's birth control rules. These apply to women who can become pregnant and men who are sexually active with women who can become pregnant.

Simplified for readability. The official criteria below are what the study team uses.

Official 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.

Study sites (6)

CA

FL

GA

MO

NY

TX