Leukemia, Acute Lymphoblastic
Conditions
Keywords
ALL, High-risk first relapse B-precursor ALL, Precursor Cell Lymphoblastic Leukemia, Neoplasms, Lymphoproliferative Disorders, Immunoproliferative Disorders, Antibodies, Bispecific
Brief summary
B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according to risk characteristics to ensure that appropriate treatment is administered to patients with high-risk of relapse. In general, pediatric treatment regimens are more intense than those employed in adults and include courses of combination chemotherapy. Standard of care chemotherapy is associated with considerable toxicity. There is a lack of novel treatment options for subjects who relapse or are refractory to treatment. Therefore, innovative therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. This study will evaluate the event-free survival (EFS) after treatment with blinatumomab when compared to standard of care (SOC) chemotherapy. The effect of blinatumomab on overall survival and reduction of minimal residual disease compared to SOC chemotherapy will also be investigated.
Detailed description
Patients will be randomized in a 1:1 ratio to receive either one cycle of blinatumomab or one block of standard high-risk consolidation chemotherapy. Blinatumomab is administered as a continuous intravenous infusion (CIVI). One cycle of blinatumomab treatment includes 4 weeks of CIVI of blinatumomab. After completing consolidation therapy, the patients should undergo alloHSCT depending on their bone marrow status. The patients will be followed up until the last subject on study is 36 months following alloHSCT or has died, whichever is first.
Interventions
DRUGBlinatumomab
15 μg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks
DRUGDexamethasone
10 mg/m\^2/day intravenous (IV) on Days 1-6
DRUGVincrisitne
1.5 mg/m\^2/day IV on Days 1 and 6
DRUGDaunorubicin
30 mg/m\^2 IV over 24 hours on Day 5
DRUGMethotrexate
1 g/m\^2 IV over 36 hours on Day 1
DRUGIfosfamide
800 mg/m\^2 IV for 1 hour on Days 2-4
DRUGPEG-asparaginase
1000 U/m\^2 IV for 2 hours or intramuscularly (IM) on Day 6
DRUGErwinia-asparaginase
In case of allergic reaction to PEG-asparaginase, participants could change to erwinia-asparaginase, 20,000 units/m2 every 48 hours for a total of 6 doses
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor acute lymphoblastic leukemia (ALL; as defined by International Berlin-Frankfurt-Muenster study group/International study for treatment of childhood relapsed ALL \[I-BFM SG/IntReALL\] criteria) * Subjects with bone marrow blast percentage \< 5% (M1) or bone marrow blast percentage \< 25% and ≥5% (M2) marrow at the time of randomization, * Age \> 28 days and \< 18 years at the time of informed consent/assent * Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated * Availability of the following material from relapse diagnosis for central analysis of minimal residual disease (MRD) by polymerase chain reaction (PCR): clone-specific primers and reference deoxyribonucleic acid (DNA), as well as primer sequences and analyzed sequences of clonal rearrangements (cases with isolated extramedullary relapse or cases with technical and/or logistic hurdles to obtain and process bone marrow material are exempt from providing this material. In these cases, central MRD analysis only by Flow is permitted).
Exclusion criteria
* Clinically relevant central nervous system (CNS) pathology requiring treatment (eg, unstable epilepsy). Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully treated prior to enrollment * Peripheral neutrophils \< 500/μL prior to start of treatment * Peripheral platelets \< 50,000/μL prior to start of treatment * Currently receiving treatment in another investigational device or drug study or less than 4 weeks since ending treatment on another investigational device or drug study(s), procedures required by IntReALL high-risk (HR) guidelines are allowed * Chemotherapy related toxicities that have not resolved to ≤ grade 2 (except for parameters defined in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis) | As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months. | EFS is calculated from the time of randomization until the date of relapse or M2 marrow (representative bone marrow aspirate or biopsy with ≥ 5% and \< 25% blasts) after having achieved a complete remission (CR), failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with investigational product (IP) or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5. |
| Kaplan Meier Estimate: EFS (Final Analysis) | At final analysis, overall median follow-up time for EFS was 51.9 months. | EFS is calculated from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with IP or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Relapse (CIR) | At final analysis, the overall maximum follow-up time was 82.0 months. | CIR estimate, presented as median months to relapse, calculated from date of achievement of first CR, using the cumulative incidence method (Fine JP, Gray RJ:1999). Deaths prior to relapse not considered related to an otherwise undocumented relapse were treated as a competing risk. Participants still alive without a date of relapse were censored at the time of last follow-up. Relapse=presence of ≥1 of the following: * isolated bone marrow relapse (M3 marrow \[representative bone marrow aspirate or biopsy with ≥25% blasts\] in the absence of extramedullary involvement) * combined bone marrow relapse (M2 \[representative bone marrow aspirate or biopsy with ≥5% and \<25% blasts\] or M3 marrow and ≥1 extramedullary manifestation of acute lymphoblastic leukemia) * central nervous system extramedullary relapse * testicular extramedullary relapse * extramedullary relapse at other sites Months were calculated as days from randomization to event/censor date, divided by 30.5. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | From first dose of IP through the last dose of IP (up to Day 29) plus 30 days. | Adverse event (AE): any untoward medical occurrence. Serious AE: an AE meeting at least 1 of the following serious criteria: fatal; life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Severity was graded according to the Common Terminology Criteria for AEs (CTCAE) version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Investigational product (IP) in the HC3 arm refers to dexamethasone, methotrexate, daunorubicin, erwinase, ifosfamide, asparaginase, and vincristine, and in the blinatumomab arm refers to blinatumomab. Treatment-related refers to the assessment of a relationship between IP and the event. |
| Number of Participants With TEAEs of Interest | From first dose of IP through the last dose of IP (up to Day 29) plus 30 days. | TEAEs of interest included capillary leak syndrome (CLS), cytokine release syndrome (CRS), decreased immunoglobulins (DI), elevated liver enzymes (ELE), embolic and thrombotic events (ETE), infections (INF), infusion reactions without considering duration (IRWCD), medication errors (ME), neurologic events (NE), neutropenia and febrile neutropenia (NFN), pancreatitis (PNC), tumor lysis syndrome, leukoencephalopathy, immunogenicity. Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. |
| Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Up to Day 29 (± 2 days). | Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Increases (↑) or decreases (↓) in laboratory value grades (Gr) from baseline (BL) to worst postbaseline (→ PB) grade are presented. NA=not available. |
| Kaplan Meier Estimate: Overall Survival (OS) | At final analysis, overall median follow-up time for OS was 55.2 months. | OS was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive. Months were calculated as days from randomization date to event/censor date, divided by 30.5. |
| Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only) | Day 1 to Day 29. | Participants receiving blinatumomab had blood samples analyzed for binding antibodies. Samples testing positive for binding antibodies were also tested for neutralizing antibodies. Participants who were binding antibody-positive or neutralizing antibody-positive post-baseline with a negative or no result at baseline are presented. |
| Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only) | Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15 | — |
| Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only) | Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15 | — |
| Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) | From the date of alloHSCT until death/censor date; median follow up time was 1742.0 days for blinatumomab and 1619.0 days for HC3. | The analysis of 100-day mortality after alloHSCT was assessed for participants who received an alloHSCT while in remission and did not receive any additional anti-leukemic treatment. 100-day mortality after alloHSCT was calculated relative to the date of alloHSCT. The 100-day mortality rate after alloHSCT was defined as the percentage of participants having died up to 100 days after alloHSCT, estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants still alive were censored at the date they were last known to be alive. |
| Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation | Up to End of Treatment (Cycle 1, Day 29) | At the end of the first treatment cycle (Day 29) a bone marrow aspiration/biopsy was performed and evaluated by the central MRD laboratory. MRD response was defined as MRD level \< 10\^-4, by polymerase chain reaction (PCR) or flow cytometry, at the end of treatment (Cycle 1 Day 29) with study drug. Participants who were part of the MRD Evaluable Set and were missing the end of treatment (Cycle 1 Day 29) assessment for a respective MRD assessment method were considered not to have achieved a response. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
This study was conducted at 48 centers across 13 countries (Europe, Australia, Israel). The first participant was enrolled on 10 November 2015. The last participant enrolled on 30 August 2019. The primary completion date was 17 July 2019 and the study completion date was 21 November 2022.
Pre-assignment details
After a 3-week screening period, participants were enrolled and randomized 1:1 into 1 of 2 treatment groups: High Risk Consolidation 3 (HC3) chemotherapy or blinatumomab. Randomization was stratified by age and bone marrow/minimal residual disease (MRD) status.
Participants by arm
| Arm | Count |
|---|---|
| HC3 Chemotherapy One week of treatment with HC3 followed by 3 weeks of no treatment. The standard intensive consolidation chemotherapy course HC3 includes dexamethasone (10 mg/m\^2/day IV on Days 1-6), vincrisitne (1.5 mg/m\^2/day IV on Days 1 and 6), daunorubicin (30 mg/m\^2 IV over 24 hours on Day 5), methotrexate (1 g/m\^2 IV over 36 hours on Day 1), ifosfamide (800 mg/m\^2 IV for 1 hour on Days 2-4), and pegylated \[PEG\]-asparaginase (1000 U/m\^2 IV for 2 hours or IM on Day 6) or, if allergic, erwinia-asparaginase (20,000 units/m\^2 IV or IM every 48 hours for a total of 6 doses). | 57 |
| Blinatumomab One 4-week cycle of blinatumomab 15 μg/m\^2/day as a continuous intravenous infusion (CIVI). | 54 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 27 | 10 |
| Overall Study | Decision by Sponsor | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 6 |
Baseline characteristics
| Characteristic | HC3 Chemotherapy | Total | Blinatumomab |
|---|---|---|---|
| Age, Continuous | 6.6 years STANDARD_DEVIATION 4.3 | 7.0 years STANDARD_DEVIATION 4.4 | 7.3 years STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 107 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 46 Participants | 96 Participants | 50 Participants |
| Sex: Female, Male Female | 34 Participants | 58 Participants | 24 Participants |
| Sex: Female, Male Male | 23 Participants | 53 Participants | 30 Participants |
| Stratification Factor: Age Category 1 to 9 years | 41 Participants | 80 Participants | 39 Participants |
| Stratification Factor: Age Category Other (< 1 year and > 9 years) | 16 Participants | 31 Participants | 15 Participants |
| Stratification Factor: Marrow/Minimal Residual Disease (MRD) M1 Marrow + MRD level < 10^-3 | 36 participants | 71 participants | 35 participants |
| Stratification Factor: Marrow/Minimal Residual Disease (MRD) M1 Marrow + MRD level ≥ 10^-3 | 17 participants | 32 participants | 15 participants |
| Stratification Factor: Marrow/Minimal Residual Disease (MRD) M2 Marrow | 4 participants | 8 participants | 4 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 28 / 57 | 11 / 54 |
| other Total, other adverse events | 48 / 52 | 54 / 54 |
| serious Total, serious adverse events | 24 / 52 | 15 / 54 |
Outcome results
Primary
Kaplan Meier Estimate: EFS (Final Analysis)
EFS is calculated from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with IP or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.
Time frame: At final analysis, overall median follow-up time for EFS was 51.9 months.
Population: FAS: randomized participants analyzed according to their randomized treatment assignment, regardless of the treatment received (final analysis population).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HC3 Chemotherapy | Kaplan Meier Estimate: EFS (Final Analysis) | 7.8 months |
| Blinatumomab | Kaplan Meier Estimate: EFS (Final Analysis) | NA months |
p-value: <0.001Stratified log-rank test
p-value: <0.001Unstratified log-rank test
95% CI: [0.2, 0.61]
95% CI: [0.22, 0.65]
95% CI: [0.2, 0.59]
Primary
Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis)
EFS is calculated from the time of randomization until the date of relapse or M2 marrow (representative bone marrow aspirate or biopsy with ≥ 5% and \< 25% blasts) after having achieved a complete remission (CR), failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with investigational product (IP) or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.
Time frame: As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.
Population: Full Analysis Set: randomized participants analyzed according to their randomized treatment assignment, regardless of the treatment received (primary analysis population).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HC3 Chemotherapy | Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis) | 7.4 months |
| Blinatumomab | Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis) | NA months |
p-value: <0.001Stratified log-rank test
p-value: 0.001Unstratified log-rank test
95% CI: [0.19, 0.66]
95% CI: [0.22, 0.7]
95% CI: [0.2, 0.64]
Secondary
Cumulative Incidence of Relapse (CIR)
CIR estimate, presented as median months to relapse, calculated from date of achievement of first CR, using the cumulative incidence method (Fine JP, Gray RJ:1999). Deaths prior to relapse not considered related to an otherwise undocumented relapse were treated as a competing risk. Participants still alive without a date of relapse were censored at the time of last follow-up. Relapse=presence of ≥1 of the following: * isolated bone marrow relapse (M3 marrow \[representative bone marrow aspirate or biopsy with ≥25% blasts\] in the absence of extramedullary involvement) * combined bone marrow relapse (M2 \[representative bone marrow aspirate or biopsy with ≥5% and \<25% blasts\] or M3 marrow and ≥1 extramedullary manifestation of acute lymphoblastic leukemia) * central nervous system extramedullary relapse * testicular extramedullary relapse * extramedullary relapse at other sites Months were calculated as days from randomization to event/censor date, divided by 30.5.
Time frame: At final analysis, the overall maximum follow-up time was 82.0 months.
Population: FAS: randomized participants analyzed according to their randomized treatment assignment, regardless of the treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HC3 Chemotherapy | Cumulative Incidence of Relapse (CIR) | 7.9 months |
| Blinatumomab | Cumulative Incidence of Relapse (CIR) | NA months |
95% CI: [0.16, 0.52]
95% CI: [0.15, 0.48]
Secondary
Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)
The analysis of 100-day mortality after alloHSCT was assessed for participants who received an alloHSCT while in remission and did not receive any additional anti-leukemic treatment. 100-day mortality after alloHSCT was calculated relative to the date of alloHSCT. The 100-day mortality rate after alloHSCT was defined as the percentage of participants having died up to 100 days after alloHSCT, estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants still alive were censored at the date they were last known to be alive.
Time frame: From the date of alloHSCT until death/censor date; median follow up time was 1742.0 days for blinatumomab and 1619.0 days for HC3.
Population: HSCT Analysis Set: participants who underwent an HSCT while in remission without any other anti-leukemic therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HC3 Chemotherapy | Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) | 5.1 percentage of participants |
| Blinatumomab | Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) | 3.9 percentage of participants |
Secondary
Kaplan Meier Estimate: Overall Survival (OS)
OS was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive. Months were calculated as days from randomization date to event/censor date, divided by 30.5.
Time frame: At final analysis, overall median follow-up time for OS was 55.2 months.
Population: FAS: randomized participants analyzed according to their randomized treatment assignment, regardless of the treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HC3 Chemotherapy | Kaplan Meier Estimate: Overall Survival (OS) | 25.6 months |
| Blinatumomab | Kaplan Meier Estimate: Overall Survival (OS) | NA months |
p-value: 0.001Stratified log-rank test
p-value: <0.001Unstratified log-rank test
95% CI: [0.16, 0.66]
95% CI: [0.16, 0.65]
Secondary
Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only)
Participants receiving blinatumomab had blood samples analyzed for binding antibodies. Samples testing positive for binding antibodies were also tested for neutralizing antibodies. Participants who were binding antibody-positive or neutralizing antibody-positive post-baseline with a negative or no result at baseline are presented.
Time frame: Day 1 to Day 29.
Population: Safety Analysis Set: participants who received protocol-specified therapy analyzed according to the treatment they received. Participants in the blinatumumab arm with a post-baseline result.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HC3 Chemotherapy | Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only) | Binding Antibody Positive | 0 participants |
| HC3 Chemotherapy | Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only) | Neutralizing Antibody Positive | 0 participants |
Secondary
Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values
Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Increases (↑) or decreases (↓) in laboratory value grades (Gr) from baseline (BL) to worst postbaseline (→ PB) grade are presented. NA=not available.
Time frame: Up to Day 29 (± 2 days).
Population: Safety Analysis Set: who received protocol-specified therapy analyzed according to the treatment they received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lipase ↑ BL Gr 0 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr 1 → PB Gr 3 | 5 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Bilirubin ↑ BL Gr 0 → PB Gr 3 | 2 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Calcium ↓ BL Gr 0 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr 1 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Creatinine ↑ BL Gr NA → PB Gr 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Potassium ↓ BL Gr 0 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Hemoglobin ↓ BL Gr 0 → PB Gr 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr NA → PB Gr 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Hemoglobin ↓ BL Gr 1 → PB Gr 3 | 4 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Alanine Aminotransferase ↑ BL Gr 0 → PB Gr 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 0 → PB Gr 3 | 7 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr 0 → PB Gr 3 | 3 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 0 → PB Gr 4 | 13 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Potassium ↓ BL Gr 0 → PB Gr 3 | 4 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 1 → PB Gr 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr 1 → PB Gr 3 | 6 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 1 → PB Gr 4 | 8 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 0 → PB Gr 3 | 2 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Alanine Aminotransferase ↑ BL Gr 1 → PB Gr 3 | 9 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 0 → PB Gr 4 | 4 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr 1 → PB Gr 4 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 1 → PB Gr 3 | 4 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Albumin ↓ BL Gr 0 → PB Gr 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 1 → PB Gr 4 | 7 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Amylase ↑ BL Gr 0 → PB Gr 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Neutrophils ↓ BL Gr 0 → PB Gr 3 | 4 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr NA → PB Gr 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Neutrophils ↓ BL Gr 0 → PB Gr 4 | 23 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Amylase ↑ BL Gr 0 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↑ BL Gr 0 → PB Gr 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Bilirubin ↑ BL Gr 0 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 0 → PB Gr 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Amylase ↑ BL Gr 1 → PB Gr 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 0 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr 0 → PB Gr 3 | 2 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 1 → PB Gr 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Potassium ↑ BL Gr 0 → PB Gr 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 1 → PB Gr 4 | 1 participants |
| HC3 Chemotherapy | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lipase ↑ BL Gr 0 → PB Gr 3 | 3 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 1 → PB Gr 4 | 2 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 1 → PB Gr 4 | 2 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Potassium ↑ BL Gr 0 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Potassium ↓ BL Gr 0 → PB Gr 3 | 5 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Potassium ↓ BL Gr 0 → PB Gr 4 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Albumin ↓ BL Gr 0 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Calcium ↓ BL Gr 0 → PB Gr 4 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Alanine Aminotransferase ↑ BL Gr 0 → PB Gr 3 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Alanine Aminotransferase ↑ BL Gr 1 → PB Gr 3 | 5 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr NA → PB Gr 3 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr 0 → PB Gr 3 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr 1 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Aspartate Aminotransferase ↑ BL Gr 1 → PB Gr 4 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr NA → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr 0 → PB Gr 3 | 4 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr 1 → PB Gr 3 | 2 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Gamma-Glutamyl Transferase ↑ BL Gr 1 → PB Gr 4 | 3 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Amylase ↑ BL Gr 0 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Amylase ↑ BL Gr 0 → PB Gr 4 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Amylase ↑ BL Gr 1 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lipase ↑ BL Gr 0 → PB Gr 3 | 2 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lipase ↑ BL Gr 0 → PB Gr 4 | 2 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Bilirubin ↑ BL Gr 0 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Bilirubin ↑ BL Gr 0 → PB Gr 4 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Creatinine ↑ BL Gr NA → PB Gr 3 | 2 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Hemoglobin ↓ BL Gr 0 → PB Gr 3 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Hemoglobin ↓ BL Gr 1 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 0 → PB Gr 3 | 6 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 0 → PB Gr 4 | 6 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Platelets ↓ BL Gr 1 → PB Gr 3 | 2 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 0 → PB Gr 3 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 0 → PB Gr 4 | 0 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 1 → PB Gr 3 | 4 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Leukocytes ↓ BL Gr 1 → PB Gr 4 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Neutrophils ↓ BL Gr 0 → PB Gr 3 | 11 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Neutrophils ↓ BL Gr 0 → PB Gr 4 | 3 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↑ BL Gr 0 → PB Gr 3 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 0 → PB Gr 3 | 3 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 0 → PB Gr 4 | 1 participants |
| Blinatumomab | Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values | Lymphocytes ↓ BL Gr 1 → PB Gr 3 | 1 participants |
Secondary
Number of Participants With TEAEs of Interest
TEAEs of interest included capillary leak syndrome (CLS), cytokine release syndrome (CRS), decreased immunoglobulins (DI), elevated liver enzymes (ELE), embolic and thrombotic events (ETE), infections (INF), infusion reactions without considering duration (IRWCD), medication errors (ME), neurologic events (NE), neutropenia and febrile neutropenia (NFN), pancreatitis (PNC), tumor lysis syndrome, leukoencephalopathy, immunogenicity. Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.
Time frame: From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Population: Safety Analysis Set: who received protocol-specified therapy analyzed according to the treatment they received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal CLS Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | IFN Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | DI Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | IFN Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious CRS Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | IRWCD Events | 4 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | DI Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | IRWCD Events Grade ≥ 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CLS Events Grade ≥ 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious IRWCD Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ELE Events | 15 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal IRWCD Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal CRS Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | IRWCD Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | IRWCD Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | INF Events | 18 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ME Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ELE Events Grade ≥ 3 | 9 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ME Events Grade ≥ 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CLS Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious ME Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CRS Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal ME Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious ELE Events | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ME Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CLS Events | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ME Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal ELE Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NE Events | 15 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | INF Events Grade ≥ 3 | 6 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NE Events Grade ≥ 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CRS Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious NE Events | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ELE Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal NE Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CLS Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NE Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ELE Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NE Events Leading to Interruption of IP | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | DI Events Grade ≥ 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ETE Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NFN Events Grade ≥ 3 | 27 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious CLS Events | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious NFN Events | 12 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NFN Events | 28 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal NFN Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ETE Events Grade ≥ 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NFN Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious ETE Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | NFN Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious DI Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | PNC Events | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal ETE Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | PNC Events Grade ≥ 3 | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CRS Events | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious PNC Events | 1 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ETE Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal PNC Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal DI Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | PNC Events Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | ETE Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | PNC Events Leading to Interruption of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | DI Events | 6 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Tumour Lysis Syndrome Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Serious INF Events | 6 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Leukoencephalopathy Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | CRS Events Grade ≥ 3 | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Immunogenicity Events | 0 participants |
| HC3 Chemotherapy | Number of Participants With TEAEs of Interest | Fatal INF Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ME Events | 1 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | IRWCD Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CLS Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CLS Events Grade ≥ 3 | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious CLS Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal CLS Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CLS Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CLS Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CRS Events | 2 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CRS Events Grade ≥ 3 | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious CRS Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal CRS Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CRS Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | DI Events | 9 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | DI Events Grade ≥ 3 | 1 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious DI Events | 1 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ETE Events Grade ≥ 3 | 2 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal DI Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ETE Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | DI Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | DI Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ELE Events | 7 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ELE Events Grade ≥ 3 | 3 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | INF Events | 25 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious ELE Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal ELE Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ELE Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ELE Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ETE Events | 4 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious ETE Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal ETE Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ETE Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | INF Events Grade ≥ 3 | 11 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious INF Events | 4 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal INF Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | IFN Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | IFN Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | IRWCD Events | 37 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | IRWCD Events Grade ≥ 3 | 2 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious IRWCD Events | 1 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal IRWCD Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | IRWCD Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | CRS Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ME Events Grade ≥ 3 | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious ME Events | 1 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal ME Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ME Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | ME Events Leading to Interruption of IP | 1 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NE Events | 26 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NE Events Grade ≥ 3 | 3 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious NE Events | 5 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal NE Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NE Events Leading to Discontinuation of IP | 2 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NE Events Leading to Interruption of IP | 3 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NFN Events | 12 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NFN Events Grade ≥ 3 | 11 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious NFN Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal NFN Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NFN Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | NFN Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | PNC Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | PNC Events Grade ≥ 3 | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Serious PNC Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Fatal PNC Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | PNC Events Leading to Discontinuation of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | PNC Events Leading to Interruption of IP | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Tumour Lysis Syndrome Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Leukoencephalopathy Events | 0 participants |
| Blinatumomab | Number of Participants With TEAEs of Interest | Immunogenicity Events | 0 participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)
Adverse event (AE): any untoward medical occurrence. Serious AE: an AE meeting at least 1 of the following serious criteria: fatal; life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Severity was graded according to the Common Terminology Criteria for AEs (CTCAE) version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Investigational product (IP) in the HC3 arm refers to dexamethasone, methotrexate, daunorubicin, erwinase, ifosfamide, asparaginase, and vincristine, and in the blinatumomab arm refers to blinatumomab. Treatment-related refers to the assessment of a relationship between IP and the event.
Time frame: From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Population: Safety Analysis Set: participants who received protocol-specified therapy analyzed according to the treatment they received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Serious TEAEs | 24 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs | 50 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs Grade ≥ 3 | 43 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Fatal TEAEs | 0 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs Leading to Interruption of IP | 2 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs | 41 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs Grade ≥ 3 | 33 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Serious TRAEs | 15 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Fatal TRAEs | 0 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs Leading to Discontinuation of IP | 0 participants |
| HC3 Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs Leading to Interruption of IP | 2 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs Leading to Discontinuation of IP | 2 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs | 45 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs | 54 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Fatal TRAEs | 0 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs Grade ≥ 3 | 33 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Serious TEAEs | 15 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs Grade ≥ 3 | 9 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Fatal TEAEs | 0 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TRAEs Leading to Interruption of IP | 5 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs Leading to Discontinuation of IP | 2 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Serious TRAEs | 9 participants |
| Blinatumomab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | TEAEs Leading to Interruption of IP | 6 participants |
Secondary
Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation
At the end of the first treatment cycle (Day 29) a bone marrow aspiration/biopsy was performed and evaluated by the central MRD laboratory. MRD response was defined as MRD level \< 10\^-4, by polymerase chain reaction (PCR) or flow cytometry, at the end of treatment (Cycle 1 Day 29) with study drug. Participants who were part of the MRD Evaluable Set and were missing the end of treatment (Cycle 1 Day 29) assessment for a respective MRD assessment method were considered not to have achieved a response.
Time frame: Up to End of Treatment (Cycle 1, Day 29)
Population: MRD Evaluable Set: participants for whom an evaluable baseline MRD marker can be found with either of the MRD assessment methods of PCR or flow cytometry.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HC3 Chemotherapy | Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation | MRD Response by PCR | 53.1 percentage of participants |
| HC3 Chemotherapy | Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation | MRD Response by Flow Cytometry | 60.0 percentage of participants |
| Blinatumomab | Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation | MRD Response by PCR | 93.9 percentage of participants |
| Blinatumomab | Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation | MRD Response by Flow Cytometry | 92.6 percentage of participants |
Comparison: MRD response by PCRp-value: <0.001Cochran-Mantel-Haenszel
Comparison: MRD response by flow cytometryp-value: <0.001Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only)
Time frame: Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Population: PK Analysis Set: participants who received any infusion of blinatumomab and had at least one PK sample collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HC3 Chemotherapy | Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only) | 1.14 L/hr/m^2 | Standard Deviation 0.836 |
Secondary
Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only)
Time frame: Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Population: Pharmacokinetic (PK) Analysis Set: participants who received any infusion of blinatumomab and had at least one PK sample collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HC3 Chemotherapy | Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only) | 884 pg/mL | Standard Deviation 969 |