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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04524455
Registration number
NCT04524455
Ethics application status
Date submitted
20/08/2020
Date registered
24/08/2020
Date last updated
8/04/2024
Titles & IDs
Public title
Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL
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Scientific 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)
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Secondary ID [1]
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20190177
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Blinatumomab
Treatment: Drugs - AMG 404
Treatment: Drugs - Dexamethasone Premedication
Experimental: Blinatumomab and AMG 404 -
Treatment: Drugs: Blinatumomab
Blinatumomab will be administered as a continuous intravenous infusion (cIV).
Treatment: Drugs: AMG 404
AMG 404 will be administered as an intravenous infusion (IV).
Treatment: Drugs: Dexamethasone Premedication
Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
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Assessment method [1]
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Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.
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Timepoint [1]
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Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
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Primary outcome [2]
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Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)
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Assessment method [2]
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A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that:
results in death,
immediately life-threatening,
requires in-patient hospitalization or prolongation of existing hospitalization,
results in persistent or significant disability/incapacity,
is a congenital anomaly/birth defect, and/or
other medically important serious AE.
AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.
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Timepoint [2]
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Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days
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Secondary outcome [1]
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Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)
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Assessment method [1]
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Hematological remissions were defined by the following criteria:
CR:
Less than 5% blasts in the bone marrow (BM)
No evidence of disease
Full recovery of peripheral blood (PB) counts:
Platelets > 100 000/µl
Absolute neutrophil count (ANC) > 1000/µl
CR with only CRh:
Less than 5% blasts in the BM
No evidence of disease
Partial recovery of PB counts:
Platelets > 50 000/µl and
ANC > 500/µl
Percentage of participants with CR/CRh were summarized along with corresponding 95% exact confidence interval (CI) using the Clopper-Pearson method.
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Timepoint [1]
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Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
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Secondary outcome [2]
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Percentage of Participants Who Achieved CR
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Assessment method [2]
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Hematological remissions were defined by the following criteria:
CR:
Less than 5% blasts in the BM
No evidence of disease
Full recovery of PB counts:
Platelets > 100 000/µl
ANC > 1000/µl
Percentage of participants with CR were summarized along with corresponding 95% exact CI using the Clopper-Pearson method.
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Timepoint [2]
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Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
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Secondary outcome [3]
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Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles
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Assessment method [3]
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Duration of CR was calculated from the date CR was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR to event/censor date, divided by 30.5.
Median time to event and 95% CI was summarized using the Kaplan-Meier (KM) method.
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Timepoint [3]
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Up to approximately 274 days
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Secondary outcome [4]
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Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles
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Assessment method [4]
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Duration of CR/CRh was calculated from the date CR/CRh was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR/CRh to event/censor date, divided by 30.5.
Median time to event and 95% CI was summarized using the KM method.
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Timepoint [4]
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Up to approximately 274 days
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Secondary outcome [5]
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Steady-state Concentrations (Css) of Blinatumomab
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Assessment method [5]
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Pharmacokinetic (PK) parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
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Timepoint [5]
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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
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Secondary outcome [6]
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Maximum Observed Concentration (Cmax) of AMG 404
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Assessment method [6]
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PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
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Timepoint [6]
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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)
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Secondary outcome [7]
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Time to Cmax (Tmax) of AMG 404
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Assessment method [7]
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PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
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Timepoint [7]
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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)
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Secondary outcome [8]
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Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404
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Assessment method [8]
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PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
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Timepoint [8]
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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)
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Secondary outcome [9]
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Number of Participants With Incidences of Anti-Blinatumomab Antibodies
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Assessment method [9]
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Only samples testing positive for anti-blinatumomab binding antibodies were to be tested for neutralizing antibodies (NAbs) as pre-specified in the protocol.
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Timepoint [9]
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Up to approximately 274 days
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Secondary outcome [10]
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Number of Participants With Incidences of Anti-AMG 404 Antibodies
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Assessment method [10]
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Only samples testing positive for anti-AMG 404 binding antibodies were to be tested for NAbs as pre-specified in the protocol.
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Timepoint [10]
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Up to approximately 274 days
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Eligibility
Key inclusion 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.
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Minimum age
18
Years
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Maximum age
99
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
2/10/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
24/01/2023
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Sample size
Target
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Accrual to date
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Final
17
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Recruitment in Australia
Recruitment state(s)
SA,VIC
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Recruitment hospital [1]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [2]
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The Royal Melbourne Hospital - Parkville
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Recruitment postcode(s) [1]
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5000 - Adelaide
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Recruitment postcode(s) [2]
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3050 - Parkville
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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United States of America
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State/province [2]
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Illinois
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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Texas
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Country [6]
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Austria
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State/province [6]
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Linz
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Country [7]
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France
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Paris
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Country [8]
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France
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State/province [8]
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Pierre Benite
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Germany
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Frankfurt am Main
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Germany
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Kiel
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Germany
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Regensburg
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Italy
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Bologna
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Italy
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State/province [13]
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Brescia
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Netherlands
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State/province [14]
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Groningen
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Spain
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State/province [15]
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Cataluña
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United Kingdom
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State/province [16]
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Amgen
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Address
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04524455
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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MD
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Address
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Amgen
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Phone
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Fax
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Email
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Contact person for public queries
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Address
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04524455
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