A Study to Assess Adverse Events and How Intravenous (IV) Pivekimab Sunirine Moves Through the Body in Pediatric Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Official title

A Phase 1b Study of the Safety and Pharmacokinetics of Pivekimab Sunirine in Pediatric Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Overview

Acute myeloid leukemia (AML) is an aggressive blood cancer, withwith few options for participants who relapse after treatment or who don't respond to treatment. This study will assess the adverse events and how pivekimab sunirine moves through the body in pediatric participants with relapsed or refractory (R/R) AML. Pivekimab sunirine is a drug being evaluated in the treatment of AML. This is an open label, single arm study, participants will be enrolled in 1 of the 3 cohorts based on their age and will receive pivekimab sunirine at a dose based on their weight. Around 18 pediatric participants with a diagnosis of AML will be enrolled in the study at approximately 30 sites around the world. Participants will receive intravenous (IV) pivekimab sunirine alone. The total study duration is approximately 28 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.

Interventions

• Drug Pivekimab Sunirine
  Intravenous

Primary outcome measures

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation [Time frame: Up to Approximately 24 Months]
• Maximum Observed Serum/Plasma Concentration (Cmax) of Intact Antibody-Drug Conjugate (ADC) [Time frame: Up to Approximately 22 Months]
• Cmax of FGN849 Payload [Time frame: Up to Approximately 22 Months]
• Area Under the Concentration-Time Curve (AUC) of Intact ADC [Time frame: Up to Approximately 22 Months]
• AUC of FGN849 payload [Time frame: Up to Approximately 22 Months]
• Time to Cmax (Tmax) of Intact ADC [Time frame: Up to Approximately 22 Months]
• Tmax of FGN849 Payload [Time frame: Up to Approximately 22 Months]

Secondary outcome measures (6)

• Percentage of Participants Achieving Complete Remission (CR) [Time frame: Up to Approximately 28 Months]
• Percentage of Participants Achieving Composite Complete Remission (CR + complete remission with incomplete recovery [CRi]) [Time frame: Up to Approximately 28 Months]
• Percentage of Participants Achieving Composite Complete Remission (CR + complete remission with partial hematological [CRh]) [Time frame: Up to Approximately 28 Months]
• Duration of Complete Remission (DOCR) [Time frame: Up to Approximately 28 Months]
• Duration of Composite Complete Remission (CR + CRi) [Time frame: Up to Approximately 28 Months]
• Duration of Composite Complete Remission (CR + CRh) [Time frame: Up to Approximately 28 Months]

Eligibility criteria

Inclusion criteria

• Must have histologically confirmed acute myeloid leukemia (AML) meeting one of the following disease criteria:

• Second or greater relapse. OR
• Disease refractory to second or subsequent line of therapy (defined as resistant disease after at least one cycle of each treatment regimen).
• Must have myeloid leukemic blasts that are CD123-positive by flow cytometry as determined by the treating institution.
• Has >= 5% myeloid leukemic blasts in bone marrow at time of relapse or refractory disease and prior to Screening for this study.
• Performance status by Lansky (< 16 years old at evaluation) or Karnofsky (>= 16 years old at evaluation) score >= 50 or ECOG score <= 2.
• May have status of central nervous system (CNS)1, CNS2, or CNS3 disease without clinical signs or neurologic symptoms suggestive of CNS leukemia, such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome. Participants receiving intrathecal therapy and no additional CNS-directed systemic therapy at study entry are eligible and may continue treatment as clinically indicated in accordance with institutional practice.
• For those participants who have not reached the age of consent, parent or legal guardian with the willingness and ability to provide informed consent and participant willing and able to give assent, as appropriate for age and country.

Exclusion criteria

• Known clinically significant cardiac disease.
• Down syndrome.
• Acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML).
• Symptomatic central nervous system (CNS3) disease
• Prior history of any severity veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) of the liver.
• Prior history of hematopoietic stem cell transplant within 6 months prior to Screening without evidence of active GvHD at the time of screening and the participant is off medications to treat or prevent either post-transplant graft-versus-host disease (GvHD) or post-transplant rejection (except for a stable dose of corticosteroids).
• Have received prior Chimeric Antigen Receptor T-cell (CAR-T) therapy.
• Any other known current malignancy requiring therapy.
• Currently receiving anticancer therapy with antineoplastic intent, including radiotherapy, systemic therapy small molecules, monoclonal antibodies, other investigational agents, or high-dose chemotherapy with the exception of intrathecal therapy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Lucile Packard Children's Hospital /ID# 276015 — Palo Alto
• New York Medical College /ID# 275597 — Valhalla
• Tristar Centennial Medical Center /ID# 275831 — Nashville

France · 2 centers

• Chu Bordeaux - Hopital Pellegrin /ID# 277645 — Bordeaux
• Hopital Armand Trousseau /ID# 276231 — Paris

South Korea · 2 centers

• Seoul National University Hospital /ID# 276978 — Seoul
• Samsung Medical Center /ID# 276979 — Seoul

Australia · 1 center

• Perth Children'S Hospital /ID# 275673 — Perth

Italy · 1 center

• Ospedale Pediatrico Bambino Gesu /ID# 275692 — Rome

Taiwan · 1 center

• National Taiwan University Hospital /ID# 276635 — Taipei

Identifiers

NCT: NCT07306832 · M25-692 · 2024-520125-36

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗