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

Official title

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)

Overview

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.

Detailed description

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

Interventions

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

Primary outcome measures

• Percentage of Participants with Complete Remission (CR) in Study Part 1 and Part 2 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Up to approximately 7 years]

Secondary outcome measures (11)

• Overall survival (OS) in Study Part 1 [Time frame: Up to approximately 7 years]
• Percentage of Participants that achieve Minimal Residual Disease (MRD) in Study Part 1 and Part 2 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Up to approximately 7 years]
• Duration of CR/CRh (DOR-CR/CRh) in Study Part 2 [Time frame: Up to approximately 7 years]
• Duration of CR/CRh/CRi (DOR-CR/CRh/CRi) in Study Part 2 [Time frame: Up to approximately 7 years]
• Event Free Survival (EFS) in Study Part 2 [Time frame: Up to approximately 7 years]
• Percentage of participants that proceed to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Study Part 2 [Time frame: Up to approximately 7 years]
• Percentage of Participants Who Experience an AE in Study Part 2 [Time frame: Up to approximately 7 years]
• Percentage of Participants Who Discontinue Study Intervention Due to an AE in Study Part 2 [Time frame: Up to approximately 7 years]

Eligibility criteria

Inclusion criteria

• 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)

Exclusion criteria

• 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

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Israel · 4 centers

• 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

Denmark · 3 centers

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

Greece · 3 centers

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

Spain · 3 centers

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

Japan · 2 centers

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

Netherlands · 2 centers

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

Italy · 1 center

• Policlinico Universitario Agostino Gemelli ( Site 1003) — Rome

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗