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)
Pivekimab SunirineVenetoclaxAzacitidineMatching Placebo for PVEK
Pivekimab Sunirine: Intravenous
Venetoclax: Orally
Azacitidine: Intravenous Or Subcutaneous
Matching Placebo for PVEK: Intravenous
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Phase 2: Complete remission (CR) — Up to Approximately 71 Months CR per modified 2022 European LeukemiaNet (ELN) response criteria in AML
Phase 3: Complete remission (CR) — Up to Approximately 71 Months CR per modified 2022 European LeukemiaNet (ELN) response criteria in AML
Phase 3: Overall Survival (OS) — Up to Approximately 71 Months The time (in number of days) from randomization to death due to any cause.
Number of Participants with Adverse Events (AEs) — Up to approximately 71 months 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.
Trial sites (32)
Facility
City
Region
Status
City of Hope National Medical Center /ID# 279568
Duarte
California
Recruiting
Moffitt Cancer Center /ID# 279192
Tampa
Florida
Recruiting
Winship Cancer Institute of Emory University /ID# 279006
Atlanta
Georgia
Recruiting
Washington University /ID# 280295
St Louis
Missouri
Recruiting
Montefiore Medical Center - Moses Campus /ID# 279399
The Bronx
New York
Recruiting
The University of Texas MD Anderson Cancer Center /ID# 279402
Houston
Texas
Recruiting
Universitaetsklinikum St. Poelten /ID# 278835
Sankt Pölten
Lower Austria
Recruiting
Hanusch-Krankenhaus /ID# 279467
Vienna
State of Vienna
Recruiting
Medizinische Universitaet Graz /ID# 278830
Graz
Styria
Recruiting
Ordensklinikum Linz Elisabethinen /ID# 278824
Linz
Upper Austria
Recruiting
Medizinische Universitaet Wien /ID# 278825
Vienna
Austria
Recruiting
Institut Paoli-Calmettes /ID# 279015
Marseille
Bouches-du-Rhone
Recruiting
Centre Hospitalier Universitaire de Bordeaux /ID# 279001
Pessac
New Aquitaine
Recruiting
Centre Hospitalier Universitaire D'Angers /ID# 280390
Angers
Pays de la Loire Region
Recruiting
Rabin Medical Center /ID# 278714
Petah Tikva
Central District
Recruiting
Tel Aviv Sourasky Medical Center /ID# 278717
Tel Aviv
Tel Aviv
Recruiting
Rambam Health Care Campus- Haifa /ID# 278719
Haifa
Israel
Recruiting
Shaare Zedek Medical Center /ID# 278712
Jerusalem
Israel
Recruiting
Hadassah Medical Center-Hebrew University /ID# 278866
Jerusalem
Israel
Recruiting
Seoul National University Bundang Hospital /ID# 279634
Seongnam-si
Gyeonggido
Recruiting
Seoul National University Hospital /ID# 279396
Seoul
Seoul Teugbyeolsi
Recruiting
Yonsei University Health System Severance Hospital /ID# 279933
Seoul
Seoul Teugbyeolsi
Recruiting
Asan Medical Center /ID# 279395
Seoul
Seoul Teugbyeolsi
Recruiting
Samsung Medical Center /ID# 279397
Seoul
Seoul Teugbyeolsi
Recruiting
Hospital Universitario Puerta De Hierro /ID# 279660
Majadahonda
Madrid
Recruiting
Clinica Universidad de Navarra - Pamplona /ID# 279516
Pamplona
Navarre
Recruiting
Hospital Universitario Virgen del Rocio /ID# 279471
Seville
Sevilla
Recruiting
Hospital General Universitario Gregorio Maranon /ID# 279479
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.