A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)
- Conditions
- bloedkankerAcute lymphocytic leukaemiaBlood Cancer
- Registration Number
- NL-OMON55298
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
• Age >= 18 years at enrollment.
• Subjects with B-precursor ALL, with any of the following:
-Refractory to primary induction or refractory to salvage therapy.
-In untreated first, second or greater relapse or refractory relapse or relapse
after salvage therapy
-Relapse at any time after allogeneic HSCT:
o Relapse is defined as achievement of CR (CR1) during upfront therapy then
relapse during or after continuation therapy.
o Refractory disease is defined as the absence of CR after standard induction
therapy.
o Refractory relapse lack of CR after first salvage therapy
o Second relapse or later relapse defined as relapse after achieving a second
CR (CR2) in first or later salvage.
• Greater than or equal to 5% blasts in the BM.
• Eastern Cooperative Oncology Group performance status (ECOG PS) <= 2.
• Negative pregnancy test in women of childbearing potential.
Refer to section 5.1 of the protocol.
• History or presence of clinically relevant CNS pathology such as epilepsy,
childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries,
dementia, Parkinson*s disease, cerebellar disease, organic brain syndrome or
psychosis.
• Presence of ALL in the CNS (confirmed by presence of blast cells in CSF) or
testes.
• Isolated extramedullary disease.
• Current autoimmune disease or history of autoimmune disease with potential
CNS involvement.
• Allogeneic HSCT within 12 weeks before the start of protocol-specified
therapy.
• Active acute or chronic graft versus host disease requiring systemic
treatment with immunosuppressive medication.
• Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular
targeted therapy) within 14 days prior to study Day 1 with the exception of
intrathecal chemotherapy and/or low dose maintenance therapy (eg vinca
alkaloids, mercaptopurine, methotrexate, or hydroxyurea). If subject is
eligible for pre phase then all low dose chemotherapy with the exception of
intrathecal chemotherapy must be discontinued prior to starting pre phase.
Tyrosine kinase inhibitors use in patients with Ph+ ALL is allowed.
• Immunotherapy (eg rituximab, alemtuzumab) within 4 weeks before start of
protocol-specified therapy. Prior treatment (given > 4 weeks prior to protocol
therapy) with any CD19-directed therapy (eg, blinatumomab, CD19-directed
chimeric antigen receptor T-cell therapy, anti-CD19 antibodies will be allowed).
Refer to section 5.2 of the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Dose-limiting toxicities (DLT)<br /><br>• Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related<br /><br>TEAEs and adverse events of interest (EOI).</p><br>
- Secondary Outcome Measures
Name Time Method <p>• CR/CRh* within the first 2 cycles and across all cycles,<br /><br>• CR within the first 2 cycles and across all cycles<br /><br>• Duration of CR<br /><br>• Duration of CR/CRh<br /><br><br /><br>• Blinatumomab PK parameters<br /><br>• AMG 404 PK parameters<br /><br><br /><br>• Anti-blinatumomab Antibodies<br /><br>• Anti-AMG 404 antibodies</p><br>