Clinical trial NCT04524455: Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Keywords: Blinatumomab
AMG 404
Leukemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-08-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.


Eligibility criteria: Inclusion Criteria

* Age ≥ 18 years at enrollment.
* Greater than or equal to 5% blasts in the bone marrow.
* Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.
* Negative pregnancy test in women of childbearing potential.

Exclusion Criteria

* Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy) within 14 days prior to study Day 1.
* Known hypersensitivity to blinatumomab or AMG 404 or to any component of the product formulation.

Primary outcomes:
measure: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
timeFrame: Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
measure: Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)
timeFrame: Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days
Secondary outcomes:
measure: Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)
timeFrame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
measure: Percentage of Participants Who Achieved CR
timeFrame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
measure: Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles
timeFrame: Up to approximately 274 days
measure: Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles
timeFrame: Up to approximately 274 days
measure: Steady-state Concentrations (Css) of Blinatumomab
timeFrame: Cohort 1: C1D1 and D8 (predose, 2 to 24 h postdose), and D11, D18 and D29; C2D1 (predose, 2 to 24 h postdose) and D29. Cohort 2a: C1D3 and D10 (predose, 2 to 48 h postdose), and D29, D30 and D31; C2D1 (predose, 2 to 24 h postdose), D13 and D29
measure: Maximum Observed Concentration (Cmax) of AMG 404
timeFrame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
measure: Time to Cmax (Tmax) of AMG 404
timeFrame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404
timeFrame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
measure: Number of Participants With Incidences of Anti-Blinatumomab Antibodies
timeFrame: Up to approximately 274 days
measure: Number of Participants With Incidences of Anti-AMG 404 Antibodies
timeFrame: Up to approximately 274 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Linz
country: Austria
facility: Ordensklinikum Linz Elisabethinen
city: Paris
country: France
facility: Hôpital Saint Louis
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Frankfurt am Main
country: Germany
facility: Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: