Feasibility Study to Evaluate Outpatient Blinatumomab in Subjects With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (ALL)

A Phase 4, Multi-center Open-label Feasibility Study to Evaluate Outpatient Blinatumomab Administration in Adult Subjects With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (ALL) in Complete Hematologic Remission

The study aims to determine the safety and feasibility of complete outpatient blinatumomab administration for subjects with minimal/measurable residual disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (ALL).

Study Overview

• Status: Recruiting
• Conditions: B-precursor Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Blinatumomab; Device: Current Wearable Heatlth Monitoring System (CWHMS)

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
    • Orange, California, United States, 92868-3201
      • Recruiting
      • University of California Irvine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Terminated
      • Mayo Clinic Florida
    • Orlando, Florida, United States, 32804
      • Completed
      • Adventist Health System/Sunbelt, Inc d/b/a AdventHealth Orlando
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Completed
      • Advocate Lutheran General Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10029
      • Completed
      • Mount Sinai Hospital
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Cancer Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Comprehensive Cancer Research Center
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Recruiting
      • Saint Francis Hospital, Inc
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures OR subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent
• Age greater than or equal to 18 years
• B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) with minimal/measurable residual disease defined as hematologic complete remission (CR) with less than 5% bone marrow blasts and meets clinical eligibility criteria to receive blinatumomab as outlined below.

• Hematologic criteria for remission as defined below:

  • Less than 5% bone marrow blasts
  • Absolute neutrophil count greater than or equal to 1.0 x10^9 L
  • Platelets greater than or equal to 50 x10^9/L (transfusion permitted)
  • Hemoglobin level greater than or equal to 90 g/L (transfusion permitted)
• Renal and hepatic function as defined below:
• Total bilirubin <3 x upper limit of normal (ULN) unless related to Gilbert's or Meulengracht disease
• Serum creatinine <1.5 x ULN. If serum creatinine ≥1.5 x ULN, then measure Glomerular Filtration Rate (GFR); subject will be eligible only if measured GFR is within normal limits.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
• Negative pregnancy test in women of childbearing potential
• Ability and willingness to wear and comply with the instructions for the use of and monitoring of the digital monitoring devices as outlined in informed consent
• Subject resides within 1 hour of ground transportation to an advanced medical care facility for the duration of the mandatory device monitoring period (MDMP)
• Adequate cellular service available during MDMP.
• Presence of an adult (greater than or equal to 18 years) caregiver(s) in the same dwelling, for 24 hours/day for the entire MDMP. Caregiver will be expected to have access to transportation
• Ability and willingness to participate in the health management of the subject and to assist with the requirements of remote digital monitoring devices during the blinatumomab infusion within the MDMP

Exclusion Criteria:

• Presence of circulating blasts
• Presence of extramedullary disease
• History of relevant central nervous system (CNS) pathology or current relevant CNS pathology (seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or coordination or movement disorders
• Current infiltration of cerebrospinal fluid (CSF) by ALL. If screening cerebrospinal fluid (CSF) demonstrates leukemic blasts, subjects must receive intrathecal treatment and demonstrate negative CSF before enrollment and starting blinatumomab infusion
• Current autoimmune disease or history of autoimmune disease with potential CNS involvement
• Allogeneic hematopoietic stem cell transplantation (HSCT) within 12 weeks before blinatumomab treatment
• Active acute or chronic graft versus host disease (GvHD) requiring systemic treatment with immunosuppressive medication
• Systemic chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis)
• Radiotherapy within 4 weeks prior to study treatment
• Known hypersensitivity to blinatumomab or to any component of the product formulation
• Active malignancy other than ALL with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix

• History of other malignancy within the past 2 years, with the following exception[s]:

  • Malignancy treated with curative intent and with no known active disease present for greater than or equal to 2 years before enrollment and felt to be at low risk for recurrence by the treating physician
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
  • Adequately treated breast ductal carcinoma in situ without evidence of disease
  • Prostatic intraepithelial neoplasia without evidence of prostate cancer
  • Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
• Currently receiving treatment with an investigational device or drug study or less than 30 days since ending treatment on an investigational device or drug study(ies)
• Active uncontrolled infection requiring therapy
• Known infection or chronic infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) or hepatitis C virus (HCV) (anti-HCV positive)
• Known positive test for human immunodeficiency virus (HIV)
• Any concurrent disease or medical condition deemed to interfere with the conduct of the study and remote digital monitoring as judged by the investigator
• Any acutely ill cardiac patients with the potential to develop life threatening arrhythmias eg, very fast atrial fibrillation
• Subjects with no cellular signal in their home
• Subjects with bi-lateral upper arm tattoos directly under the area of Current Wearable Health Monitoring System (CWHMS) application (Current Health wearable device)
• Subjects with a known allergy to any of the device component materials
• Subjects with open wounds on both arms directly under the area of CWHMS application (Current Health wearable device) or with injuries to both arms
• Subjects with an upper arm circumference of less than 20 cm or greater than 50 cm
• Subjects with an implantable defibrillator
• Subjects unwilling to wear the CWHMS (Current Health wearable device, axillary temperature patch) during the mandatory monitoring period (MDMP) in cycles 1 and 2
• Subjects with excessive scarring directly under the area of CWHMS (Current Health wearable device) application
• Subjects who cannot have their blood pressure (BP) measured in both arms (or wrists) eg due to atrio-venous shunt, risk of lymphedema or peripherally inserted central catheter line
• Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 48 hours after the last dose of protocol-specified therapy
• Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 48 hours after the last dose of protocol-specified therapy Refer to Section 11.5 for additional contraceptive information
• Female subjects of childbearing potential with a positive pregnancy test assessed at Screening by a serum pregnancy test and/or urine pregnancy test
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, patient reported outcomes [PROs]) to the best of the subject and investigator's knowledge

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinatumomab	Drug: Blinatumomab; Participants will receive blinatumomab continuous IV infusion for a maximum of 4 cycles. Each cycle is 6 weeks in duration consisting of 4 weeks of treatment and 2 weeks of rest.; Other Names: Blincyto; AMG 103; Device: Current Wearable Heatlth Monitoring System (CWHMS); The study will use the CWHMS device to monitor participants' vital signs while they are at home.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycle 1: Incidence of grade 3 and/or 4 adverse events of special interest	Adverse events of Special Interest (AESI): neurotoxicity (NT) and cytokine release syndrome (CRS).	Day 1 to 3 of Cycle 1 (each cycle is 6 weeks)
Cycle 2: Incidence of grade 3 and/or 4 adverse events of special interest	Adverse events of Special Interest (AESI): neurotoxicity (NT) and cytokine release syndrome (CRS).	Day 1 to 2 of Cycle 2 (each cycle is 6 weeks)
Cycle 1: Incidence of any adverse events requiring hospitalization		Day 1 to 3 of Cycle 1 (each cycle is 6 weeks)
Cycle 2: Incidence of any adverse events requiring hospitalization		Day 1 to 2 of Cycle 2 (each cycle is 6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time (in minutes) from first onset of fever, hypotension, hypoxia, other grade 3 or 4 vital sign including seizure or neurological change (grade 3-limiting self-care activities of daily living to therapeutic intervention		Day 1 to 3 of Cycle 1, and Day 1 to 2 of Cycle 2 (each cycle is 6 weeks)
Incidence of treatment emergent Adverse events		Up to 6 months
Incidence of Adverse events of Special interest	Adverse events of Special Interest (AESI): neurotoxicity (NT) and cytokine release syndrome (CRS).	Up to 6 Months
Severity of treatment emergent adverse events	The investigator will make an assessment of severity for each adverse event reported during the study. The assessment of severity will be based on the Common Terminology Criteria for Adverse Events version 5.0.	Up to 6 months
Severity of adverse events of special interest	Adverse events of Special Interest (AESI): neurotoxicity (NT) and cytokine release syndrome (CRS). The investigator will make an assessment of severity for each adverse event reported during the study. The assessment of severity will be based on the Common Terminology Criteria for Adverse Events version 5.0.	Up to 6 months
Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30		Prior to treatment on Day 1 of Cycle 1 and 2 (each cycle is 6 weeks)
Incidence of treatment emergent adverse events that resulted in hospitalizations		Up to 6 months
Incidence of treatment emergent adverse events that resulted in surgeries		Up to 6 months
Incidence of treatment emergent adverse events that resulted in the use of concomitant medications		Up to 6 months
Incidence of treatment emergent adverse events that resulted in the use of device/procedure intervention.		Up to 6 months

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2021
• Primary Completion (Estimated): December 28, 2025
• Study Completion (Estimated): December 28, 2025

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: August 6, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Leukemia; Blinatumomab; Acute lymphoblastic leukemia; B-precursor Acute Lymphoblastic Leukemia; Minimal/Measurable Residual Disease; Bi-specific T-cell engager
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplastic Processes; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasm, Residual; Antineoplastic Agents; Blinatumomab
• Other Study ID Numbers: 20190014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes