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

Phase 4

Terminated

Conditions: B-precursor Acute Lymphoblastic Leukemia

Interventions: Drug: Blinatumomab
Device: Current Wearable Heatlth Monitoring System (CWHMS)

Registration Number: NCT04506086

Lead Sponsor: Amgen

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Blinatumomab	Current Wearable Heatlth Monitoring System (CWHMS)	-
Blinatumomab	Blinatumomab	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Grade 3 and/or 4 Cytokine Release Syndrome (CRS), Neurotoxicity (NT) or Any Adverse Events Resulting in Hospitalization During MDMP	Cycle 1: Day 1 to Day 3; Cycle 2: Day 1 and Day 2	Adverse event were graded using the Common Terminology Criteria for Adverse Events, (CTCAE) v5.0 grading Scale. Grade 3 events were defined as severe or medically significant but not immediately life-threatening; grade 4 events were defined as life-threatening consequences; urgent intervention indicated. CSR is a heightened T-cell activation and release of pro inflammatory cytokines. NT signs include encephalopathy, delirium, aphasia, lethargy, difficulty concentrating, agitation, tremor, seizures, and, rarely, cerebral edema.

Secondary Outcome Measures

Name	Time	Method
Time to Therapeutic Intervention (TTI) During MDMP	Cycle 1: Day 1 to Day 3; Cycle 2: Day 1 and Day 2	TTI was calculated for all the valid alarm triggers which lead to an intervention as duration (in minutes) from time of the device alert (alarm triggered) to the time of initiation of the therapeutic intervention. Therapeutic intervention was any measurable action taken by the participants or performed on the participants as a result of the 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 \[ADL\]).
Number of Participants Who Experienced TEAEs That Resulted in Hospitalization, Surgeries, Use of Concomitant Medications or Use of Device/Procedure Intervention	Up to a maximum of 193 days	Concomitant therapies are any concomitant medications or treatments deemed necessary to provide adequate supportive care except for: Any anti-tumor therapy other than the protocol-specified therapy (ie, radiation therapy, immunotherapy, cytotoxic and/or cytostatic drugs); Chronic systemic (\> 7 days) high-dose corticosteroid therapy (dexamethasone \> 24 mg/day or equivalent); any other immunosuppressive therapies (except for transient use of corticosteroids); Any other investigational agent. Intervention is any measurable action taken by the subject or performed on the subject as a result of the onset of a TEAE.
Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Adverse Events of Interest (EOIs)	Up to a maximum of 193 days	TEAEs were defined as adverse events starting on or after first dose of blinatumomab. EOIs referred in particular to CRS, infections and neurologic events.
Change From Baseline to Cycle 2 Day 1 in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients (QLQ-C30) Global Health Status/ Quality of Life Score	Baseline and Cycle 2 Day 1	The EORTC QLQ-C30 is a 30-item questionnaire that assesses the health related quality of life of cancer patients participating in clinical trials. The EORTC QLQ-C30 forms a global health status (GHS)/quality of life (QoL) scale, 5 functional domains (physical, role, emotional, cognitive and social), and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales/items measures get mapped to a common range from 0 to 100. A high scale score represents a higher response level. Thus, a negative change for the global health status/QoL scale represents a lower QoL, a negative change for a functional scale represents a lower level of functioning, a positive change for a symptom scale/item represents a higher level of symptomatology/problems.

Trial Locations

Locations (12): City of Hope National Medical Center
🇺🇸
Duarte, California, United States
University of California Los Angeles
🇺🇸
Los Angeles, California, United States
University of California Irvine
🇺🇸
Orange, California, United States
Mayo Clinic
🇺🇸
Jacksonville, Florida, United States
Adventist Health System/Sunbelt, Inc d/b/a AdventHealth Orlando
🇺🇸
Orlando, Florida, United States
Advocate Lutheran General Hospital
🇺🇸
Park Ridge, Illinois, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
University of Rochester Cancer Center
🇺🇸
Rochester, New York, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Saint Francis Hospital, Inc
🇺🇸
Greenville, South Carolina, United States
University of Virginia Health System
🇺🇸
Charlottesville, Virginia, United States