Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Официальное название

Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-rearranged or NPM1-mutant Relapsed/Refractory Acute Myeloid Leukemia

Обзор

The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.

Вмешательства

• Препарат Ziftomenib
  Oral administration
• Препарат Fludarabine
  Intravenous infusion
• Препарат Idarubicin
  Intravenous infusion
• Препарат Cytarabine
  Intravenous Infusion
• Препарат Gilteritinib
  Oral administration
• Биопрепарат Granulocyte colony-stimulating factor
  Subcutaneous injection

Первичные конечные точки

• Rate of dose limiting toxicities (DLTs) per dose level [Срок оценки: During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)]
• Descriptive statistics of adverse events [Срок оценки: First dose of ziftomenib up to and including 28 days after last dose of ziftomenib, or if the patient is lost to follow-up, whichever comes first]

Вторичные конечные точки (12)

• Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2 [Срок оценки: Up to 12 months following discontinuation of treatment]
• Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3 [Срок оценки: Up to 12 months following discontinuation of treatment]
• Composite complete remission (CRc) rate [Срок оценки: Up to 12 months following discontinuation of treatment]
• Morphologic leukemia-free state (MLFS) rate [Срок оценки: Up to 12 months following discontinuation of treatment]
• OS [Срок оценки: Up to 12 months following discontinuation of treatment]
• 6-month OS [Срок оценки: Up to 6 months following discontinuation of treatment]
• Median EFS [Срок оценки: Up to 12 months following discontinuation of treatment]
• 6-month EFS [Срок оценки: Up to 6 months following discontinuation of treatment]
• DOR [Срок оценки: Up to 12 months following discontinuation of treatment]
• MRD assessment [Срок оценки: Up to 12 months following discontinuation of treatment]
• HSCT [Срок оценки: Up to 12 months following discontinuation of treatment]
• Transfusion independence [Срок оценки: Up to 12 months following discontinuation of treatment]

Критерии участия

Критерии включения

• Has been diagnosed with relapsed/refractory AML.
• Has a documented NPM1 mutation or KMT2A rearrangement.
• Has a documented FLT3 mutation (cA-3 only).
• Has an Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
• Has adequate hepatic and renal function as defined per protocol.
• Has an ejection fraction above a protocol defined limit.
• Participant, or legally authorized representative, must be able to understand and provide written informed consent prior to the first screening procedure.
• Has agreed to use contraception as defined per protocol.

Критерии исключения

• Has a diagnosis of acute promyelocytic leukemia or blast chronic myeloid leukemia.
• Has clinically active central nervous system leukemia.
• Has an active and uncontrolled infection.
• Has a mean corrected QT interval (QTcF) > 480ms.
• Has uncontrolled intercurrent illness, including, but not limited to protocol defined cardiac disease.
• Has received radiation, chemotherapy, immunotherapy, or any other anticancer therapy including investigational therapy <14 days or within 5 drug half-lives prior to the first dose of study intervention.
• Has had major surgery within 4 weeks prior to the first dose of study intervention.
• Has received a hematopoietic stem cell transplant (HSCT) and has not previously had adequate recovery per protocol defined criteria.
• Has active graft-versus-host disease (GvHD) and or on immunosuppressive drugs for the treatment of GvHD
• Participant is pregnant or lactating.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 38 центров

• Banner MD Anderson Cancer Center — Gilbert
• USC Norris Comprehensive Cancer Center — Los Angeles
• UCLA Health - Bowyer Oncology Center — Los Angeles
• UC Irvine Health Chao Family Comprehensive Cancer Center — Orange
• University of California San Francisco — San Francisco
• Colorado Blood Cancer Institute — Denver
• Smilow Cancer Hospital at Yale New Haven — New Haven
• Emory Healthcare - The Emory Clinic — Atlanta
• … и ещё 30 центров

Испания · 4 центра

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Universitario Central de Asturias — Oviedo
• Hospital Universitario Virgen del Rocío — Seville
• Hospital Universitari y Politecnic La Fe — Valencia

Италия · 3 центра

• IRCCS Azienda Ospedaliero-Universitaria do Bologna - Policlinico di Sant'Orsola — Bologna
• Ospedale Santa Maria delle Croci — Ravenna
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma

Идентификаторы

NCT: NCT06001788 · KO-MEN-008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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