Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL

Acute Lymphoblastic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04524455
• Other study ID #: 20190177
• Status: Completed
• Phase: Phase 1
• Start date: October 2, 2020
• Est. completion date: January 24, 2023

Study information

• Verified date: October 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: January 24, 2023
• Est. primary completion date: January 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Blinatumomab
Blinatumomab will be administered as a continuous intravenous infusion (cIV).
• AMG 404
AMG 404 will be administered as an intravenous infusion (IV).
• Dexamethasone Premedication
Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Austria	Ordensklinikum Linz Elisabethinen	Linz
France	Hôpital Saint Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
Germany	Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main	Frankfurt am Main
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Universitaetsklinikum Regensburg	Regensburg
Italy	Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi	Bologna
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Cataluña
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña
United Kingdom	University College London	London
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	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.	Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
Primary	Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)	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.	Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days
Secondary	Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)	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.	Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Secondary	Percentage of Participants Who Achieved CR	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.	Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Secondary	Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles	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.	Up to approximately 274 days
Secondary	Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles	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.	Up to approximately 274 days
Secondary	Steady-state Concentrations (Css) of Blinatumomab	Pharmacokinetic (PK) parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.	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
Secondary	Maximum Observed Concentration (Cmax) of AMG 404	PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.	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)
Secondary	Time to Cmax (Tmax) of AMG 404	PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.	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)
Secondary	Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404	PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.	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)
Secondary	Number of Participants With Incidences of Anti-Blinatumomab Antibodies	Only samples testing positive for anti-blinatumomab binding antibodies were to be tested for neutralizing antibodies (NAbs) as pre-specified in the protocol.	Up to approximately 274 days
Secondary	Number of Participants With Incidences of Anti-AMG 404 Antibodies	Only samples testing positive for anti-AMG 404 binding antibodies were to be tested for NAbs as pre-specified in the protocol.	Up to approximately 274 days

External Links

•   AmgenTrials clinical trials website