A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)

Официальное название

A Phase 2/3, Randomized, Open-Label, Comparison Study of MK-1045 Versus Blinatumomab in Participants With Relapsed or Refractory CD19+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Обзор

Researchers are looking for new ways to treat people with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) that is CD19 positive using a medicine called MK-1045. MK-1045 is an immunotherapy, which is a treatment that helps the immune system fight cancer. This trial will compare MK-1045 to a standard immunotherapy called blinatumomab. The goals of this trial are to learn if more people who receive MK-1045 have no cancer cells in their bone marrow compared to people who receive blinatumomab and if people who receive MK-1045 live longer compared to people who receive blinatumomab.

Подробное описание

This study has 2 parts: Part 1 is a dose optimization phase of MK-1045. Part 2 is a randomized phase comparing the efficacy and safety of MK-1045 versus blinatumomab and will use the recommended dose of MK-1045 determined in Part 1

Вмешательства

• Биопрепарат MK-1045
  Intravenous administration
• Биопрепарат Blinatumomab
  Intravenous administration
• Препарат Acetaminophen
  Oral administration as a premedication
• Препарат Diphenhydramine
  Intravenous administration as a premedication
• Препарат Dexamethasone
  Intravenous administration as a premedication
• Препарат Tocilizumab
  Intravenous administration as a rescue medication
• Препарат Siltuximab
  Intravenous administration as a rescue medication
• Препарат Avtozma
  Intravenous administration as a rescue medication
• Препарат Tyenne
  Intravenous administration as a rescue medication

Первичные конечные точки

• Percentage of Participants with Complete Remission (CR) in Study Part 1 and Part 2 [Срок оценки: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)]
• Percentage of Participants Who Experience an Adverse Event (AE) in Study Part 1 [Срок оценки: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)]
• Percentage of Participants Who Discontinue Study Intervention Due to an AE in Study Part 1 [Срок оценки: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)]
• Overall Survival (OS) in Study Part 2 [Срок оценки: Up to approximately 7 years]

Вторичные конечные точки (11)

• Overall survival (OS) in Study Part 1 [Срок оценки: Up to approximately 7 years]
• Percentage of Participants that achieve Minimal Residual Disease (MRD) in Study Part 1 and Part 2 [Срок оценки: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)]
• Percentage of Participants that achieve CR/CR with partial hematologic recovery (CRh)/CR with incomplete count recovery (CRi) in Study Part 1 and Part 2 [Срок оценки: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)]
• Percentage of Participants with CR or CRh in Study Part 2 [Срок оценки: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)]
• Duration of CR (DOR-CR) in Study Part 2 [Срок оценки: Up to approximately 7 years]
• Duration of CR/CRh (DOR-CR/CRh) in Study Part 2 [Срок оценки: Up to approximately 7 years]
• Duration of CR/CRh/CRi (DOR-CR/CRh/CRi) in Study Part 2 [Срок оценки: Up to approximately 7 years]
• Event Free Survival (EFS) in Study Part 2 [Срок оценки: Up to approximately 7 years]
• Percentage of participants that proceed to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Study Part 2 [Срок оценки: Up to approximately 7 years]
• Percentage of Participants Who Experience an AE in Study Part 2 [Срок оценки: Up to approximately 7 years]
• Percentage of Participants Who Discontinue Study Intervention Due to an AE in Study Part 2 [Срок оценки: Up to approximately 7 years]

Критерии участия

Критерии включения

• Has a confirmed diagnosis of relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) with 5% or more lymphoblasts in the bone marrow
• Has CD19+ disease, confirmed by local flow cytometry and/or immunohistochemistry testing at the time of enrollment
• Has Philadelphia-negative disease, confirmed by testing, at the time of enrollment
• Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)

Критерии исключения

• Has Burkitt's leukemia
• History or presence of clinically relevant central nervous system (CNS) diseases such as epilepsy, hemorrhagic/ischemic stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
• Has active acute graft versus host disease (GvHD) or chronic GvHD. NOTE: Participants who have received CNI for GvHD within 4 weeks before the first dose of study intervention are also excluded
• History of serious cardiovascular and cerebrovascular diseases.
• HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Received prior treatment with blinatumomab within 12 weeks for Part 1 and 24 weeks for Part 2 before the first dose of study intervention (individuals known to be refractory or intolerant to blinatumomab are to be excluded). Refractory to blinatumomab is defined as failure to achieve a response after at least 2 cycles of previous blinatumomab treatment
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
• Known additional malignancy that is progressing or has required active treatment within the past 2 years
• Isolated extramedullary disease (EMD)
• Active autoimmune disease unrelated to ALL that has required systemic treatment in the past 2 years or history of autoimmune disease with potential CNS involvement
• Active infection requiring systemic therapy
• Has not adequately recovered from major surgery or have ongoing surgical complications

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Израиль · 4 центра

• Rambam Health Care Campus ( Site 0903) — Haifa
• Haddasah Medical Center ( Site 0900) — Jerusalem
• Sheba Medical Center ( Site 0902) — Ramat Gan
• Sourasky Medical Center. ( Site 0904) — Tel Aviv

Дания · 3 центра

• Rigshospitalet ( Site 0802) — Copenhagen
• Aarhus Universitetshospital. Hæmatologisk afdeling ( Site 0804) — Aarhus Nord
• Odense Universitetshospital ( Site 0801) — Odense

Греция · 3 центра

• Evangelismos General Hospital of Athens ( Site 5100) — Athens
• General Hospital of Athens "Laiko" ( Site 5101) — Athens
• University Hospital of Ioannina ( Site 5103) — Ioannina

Испания · 3 центра

• Institut Català d'Oncologia (ICO) - Badalona ( Site 3001) — Badalona
• HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 3009) — Madrid
• Hospital Universitario de Salamanca ( Site 3002) — Salamanca

Япония · 2 центра

• Tokyo Metropolitan Komagome Hospital ( Site 2106) — Bunkyo
• Toranomon Hospital ( Site 2101) — Minato

Нидерланды · 2 центра

• Radboud UMC ( Site 2003) — Geert Grooteplein-Zuid 8
• Amsterdam UMC ( Site 2001) — Amsterdam

Италия · 1 центр

• Policlinico Universitario Agostino Gemelli ( Site 1003) — Rome

Идентификаторы

NCT: NCT07570173 · 1045-005 · MK-1045-005 · 2025-522267-15-00 · U1111-1322-4387

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗