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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04524455
Registration number
NCT04524455
Ethics application status
Date submitted
20/08/2020
Date registered
24/08/2020
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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0
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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0
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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
Years
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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
NA
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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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Country [2]
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United States of America
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State/province [2]
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Illinois
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Country [3]
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United States of America
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State/province [3]
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New York
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Country [4]
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United States of America
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State/province [4]
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Ohio
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Country [5]
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United States of America
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State/province [5]
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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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State/province [7]
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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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Country [9]
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Germany
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State/province [9]
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Frankfurt am Main
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Country [10]
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Germany
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State/province [10]
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Kiel
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Country [11]
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Germany
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State/province [11]
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Regensburg
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Country [12]
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Italy
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State/province [12]
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Bologna
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Country [13]
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Italy
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State/province [13]
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Brescia
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Country [14]
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Netherlands
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State/province [14]
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Groningen
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Country [15]
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Spain
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State/province [15]
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Cataluña
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Country [16]
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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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Country
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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/study/NCT04524455
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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MD
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Address
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Amgen
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
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When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
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Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/55/NCT04524455/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/55/NCT04524455/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT04524455