B-precursor Acute Lymphoblastic Leukemia
Conditions
Keywords
Blinatumomab, Leukemia, Acute lymphoblastic leukemia, B-precursor Acute Lymphoblastic Leukemia, Minimal/Measurable Residual Disease, Bi-specific T-cell engager
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).
Interventions
DRUGBlinatumomab
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.
DEVICECurrent Wearable Heatlth Monitoring System (CWHMS)
The study will use the CWHMS device to monitor participants' vital signs while they are at home.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
A total of 10 participants were enrolled in the United States from August 2021 to July 2024. This study was terminated by Amgen because of strategic reasons (slow enrollment) and not because of safety concerns.
Pre-assignment details
Participants were administered blinatumomab as a continuous intravenous infusion (CiVI) in 2 mandatory cycles. Each cycle lasted 6 weeks (4 weeks of CiVI and 2-week treatment-free). Participants then had the option to continue for 2 additional cycles. Mandatory monitoring period (MDMP) was defined as the first 3 days of Cycle 1 and the first 2 days of Cycle 2. During MDMP, participants wore the current wearable health monitoring system to measure vital signs 24 hours a day.
Participants by arm
| Arm | Count |
|---|---|
| Blinatumomab Participants received 28 ug/day blinatumomab as a CiVI in two 6-week cycles. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Blinatumomab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 4 / 10 |
Outcome results
Primary
Number of Participants With Grade 3 and/or 4 Cytokine Release Syndrome (CRS), Neurotoxicity (NT) or Any Adverse Events Resulting in Hospitalization During MDMP
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.
Time frame: Cycle 1: Day 1 to Day 3; Cycle 2: Day 1 and Day 2
Population: Safety Analysis Set included all enrolled participants who received at least 1 dose of blinatumomab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Blinatumomab | Number of Participants With Grade 3 and/or 4 Cytokine Release Syndrome (CRS), Neurotoxicity (NT) or Any Adverse Events Resulting in Hospitalization During MDMP | 2 Participants |
Secondary
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
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.
Time frame: Baseline and Cycle 2 Day 1
Population: Patient-Reported Outcomes (PRO) Analysis Set included all participants in the safety analysis set with a non-missing baseline and at least 1 non-missing post-baseline result for EORTC QLQ-C30.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinatumomab | 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 | EORTC QLQ-C30 Global Health Status/QoL Score | -8.333 score on a scale | Standard Deviation 11.785 |
| Blinatumomab | 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 | EORTC QLQ-C30 Functional Scales Score | -12.778 score on a scale | Standard Deviation 12.222 |
| Blinatumomab | 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 | EORTC QLQ-C30 Symptoms Scales Score | 4.487 score on a scale | Standard Deviation 6.743 |
Secondary
Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Adverse Events of Interest (EOIs)
TEAEs were defined as adverse events starting on or after first dose of blinatumomab. EOIs referred in particular to CRS, infections and neurologic events.
Time frame: Up to a maximum of 193 days
Population: Safety Analysis Set included all enrolled participants who received at least 1 dose of blinatumomab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Blinatumomab | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Adverse Events of Interest (EOIs) | TEAEs | 10 Participants |
| Blinatumomab | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Adverse Events of Interest (EOIs) | EOIs | 8 Participants |
Secondary
Number of Participants Who Experienced TEAEs That Resulted in Hospitalization, Surgeries, Use of Concomitant Medications or Use of Device/Procedure Intervention
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.
Time frame: Up to a maximum of 193 days
Population: Safety Analysis Set included all enrolled participants who received at least 1 dose of blinatumomab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Blinatumomab | Number of Participants Who Experienced TEAEs That Resulted in Hospitalization, Surgeries, Use of Concomitant Medications or Use of Device/Procedure Intervention | Hospitalizations | 3 Participants |
| Blinatumomab | Number of Participants Who Experienced TEAEs That Resulted in Hospitalization, Surgeries, Use of Concomitant Medications or Use of Device/Procedure Intervention | Surgeries | 0 Participants |
| Blinatumomab | Number of Participants Who Experienced TEAEs That Resulted in Hospitalization, Surgeries, Use of Concomitant Medications or Use of Device/Procedure Intervention | Use of concomitant medications | 9 Participants |
| Blinatumomab | Number of Participants Who Experienced TEAEs That Resulted in Hospitalization, Surgeries, Use of Concomitant Medications or Use of Device/Procedure Intervention | Use of device/procedure intervention | 3 Participants |
Secondary
Time to Therapeutic Intervention (TTI) During MDMP
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 \[ADL\]).
Time frame: Cycle 1: Day 1 to Day 3; Cycle 2: Day 1 and Day 2
Population: Primary Analysis Set included all participants who received at least 1 dose of blinatumomab for whom the outpatient monitoring during blintumomab infusion was established.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinatumomab | Time to Therapeutic Intervention (TTI) During MDMP | 14.98 minutes | Standard Deviation 26.76 |