Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute Lymphoblastic Leukemia
Brief summary
The objectives of the study are to assess the safety and tolerability of a single dose of SHP674 in Japanese participants (dose confirmation) in the tolerability assessment period of Part 1 and to assess the safety, pharmacokinetics and efficacy of SHP674 dose in Part 2 (found to be tolerated in Part 1) in the treatment of newly diagnosed untreated acute lymphoblastic leukemia (ALL) in Japanese participants.
Interventions
BIOLOGICALSHP674
SHP674: powder for solution for injection, IV (administered by 1 to 2 hours of drip infusion), dose determination : if BSA ≥0.6 m\^2: 2500 IU/m\^2 every 14 days if BSA \<0.6 m\^2: 82.5 IU/kg every 14 days
Sponsors
Kyowa Kirin Co., Ltd.
ADIR, a Servier Group company
Institut de Recherches Internationales Servier
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The intervention study model is sequential in results section of record.
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Age 1 to ≤21 years at the time of informed consent; * Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2; * Newly diagnosed, untreated precursor B-cell ALL * No prior therapy for malignant tumor such as chemotherapy and radiation therapy before signing the informed consent; * Life expectancy of at least 6 months from the date of enrollment;
Exclusion criteria
* Mature B-cell ALL ; Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL * Preexisting known coagulopathy ; * History of pancreatitis; * Continuous use of corticosteroids; * Prior treatment or possible prior treatment with an L-asparaginase preparation; * History of sensitivity to polyethylene glycol (PEG) or PEG-based drugs; * Pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period | Up to 30 days after last dose of study drug (approximately 49 weeks) | An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE. |
| Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674 | 14 days after the first dose of SHP674 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674 | 14 days after the first dose of SHP674 | — |
| Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose | — |
| Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) | Predose and 25 days post dose (Part 1 and Part 2) | — |
| Event-free Survival Rate at 1 Year After the Start of Study Treatment | 1 year after the start of study treatment (from first dose up to 12 months) | Event-free survival rate is defined as percentage of subjects who did not experience any event and survived at 1 year after the start of study treatment. |
| Survival Rate at 1 Year After the Start of Study Treatment | 1 year after the start of study treatment (from first dose up to 12 months) | Survival rate is defined as the percentage of subjects who survived at 1 year after the start of study treatment. |
| Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) | Predose and 25 days post dose (Part 1 and part 2) | — |
Countries
Japan
Participant flow
Recruitment details
Participants were enrolled at 8 investigative sites in Japan from 17 October 2019 to 18 January 2021. Data is reported up to primary completion date, 12 February 2021.
Pre-assignment details
A total of 28 participants were enrolled, 3 into Part 1 and 25 into Part 2, of which 26 participants were treated, 3 in Part 1 and 23 in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4) in the 5-week tolerability assessment period, Day 2 of re-induction therapy (conducted twice) in the 36-week treatment period. | 3 |
| Part 2: SHP674 Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (SR: IA2/IR: IA4), Day 2 of re-induction therapy (conducted twice) in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674, 2500 IU/m\^2 (if BSA ≥0.6 m\^2) or 82.5 IU/kg (if BSA \<0.6 m\^2) IV on Day 12 of Remission induction therapy (IA4), Day 38 of early consolidation therapy, Day 6 of consolidation therapies (HR3, HR2), Day 7 of consolidation therapy (HR1), Day 2 of re-induction therapy (conducted thrice) in the 45-week treatment period. | 23 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Enrolled but not treated | 0 | 1 |
| Overall Study | Screen failures | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: SHP674 | Total | Part 2: SHP674 |
|---|---|---|---|
| Age, Continuous | 10.2 years STANDARD_DEVIATION 2.63 | 7.1 years STANDARD_DEVIATION 4.7 | 6.7 years STANDARD_DEVIATION 4.79 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 26 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 3 participants | 26 participants | 23 participants |
| Sex: Female, Male Female | 2 Participants | 13 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 13 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 23 |
| other Total, other adverse events | 3 / 3 | 23 / 23 |
| serious Total, serious adverse events | 1 / 3 | 10 / 23 |
Outcome results
Primary
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period
An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE.
Time frame: Up to 30 days after last dose of study drug (approximately 49 weeks)
Population: SAF (Safety Analysis Set) included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As pre-specified in the protocol, this outcome measure is analyzed only for Part 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: SHP674 | Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period | TEAEs | 3 Participants |
| Part 1: SHP674 | Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period | SHP-674-Related TEAEs | 3 Participants |
Primary
Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674
Time frame: 14 days after the first dose of SHP674
Population: FAS (Full Analysis Set) included all participants who were enrolled and received SHP674 in Part 2 of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: SHP674 | Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674 | 100.0 participants |
Secondary
Event-free Survival Rate at 1 Year After the Start of Study Treatment
Event-free survival rate is defined as percentage of subjects who did not experience any event and survived at 1 year after the start of study treatment.
Time frame: 1 year after the start of study treatment (from first dose up to 12 months)
Population: The analysis was performed on the safety set analysis, defined as the set of all subjects who had received at least one dose of SHP674 in Part 1 or Part 2 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: SHP674 | Event-free Survival Rate at 1 Year After the Start of Study Treatment | 3 Participants |
| Part 2: SHP674 | Event-free Survival Rate at 1 Year After the Start of Study Treatment | 23 Participants |
Secondary
Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674
Time frame: 14 days after the first dose of SHP674
Population: SAF included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study. As pre-specified in the protocol, this outcome measure is analyzed only for Part 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: SHP674 | Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674 | 100.0 percentage of participants |
Secondary
Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL
Time frame: Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose
Population: FAS included all participants who were enrolled and received SHP674 in Part 2 of the study. Number analyzed indicates the number of participants analyzed at the specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 1 (pre-dose) | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 1 (5 mins post dose) | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 1 (4 hours post dose) | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 1 (24 hours post dose) | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 2 post dose | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 4 post dose | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 11 post dose | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 14 post dose | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 18 post dose | 95.5 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | ≥0.1 IU/mL: Day 25 post dose | 50.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL : Day 1 (pre-dose) | 100.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 1 (5 mins post dose) | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 1 (4 hours post dose) | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 1 (24 hours post dose) | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 2 post dose | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 4 post dose | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 11 post dose | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 14 post dose | 0.0 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 18 post dose | 4.5 percentage of participants |
| Part 1: SHP674 | Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | <0.1 IU/mL: Day 25 post dose | 50.0 percentage of participants |
Secondary
Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2)
Time frame: Predose and 25 days post dose (Part 1 and Part 2)
Population: Immunogenicity analysis set (IMAS) included all participants who had received at least one dose of SHP674 in Part 1 or Part 2 of the study and had at least one evaluable post-dose sample. If the pre-dose sample was missing it was considered negative.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: SHP674 | Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) | Pre-existing ADA positive | 0 Participants |
| Part 1: SHP674 | Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) | Seroconversion upon tretament | 0 Participants |
| Part 2: SHP674 | Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) | Pre-existing ADA positive | 4 Participants |
| Part 2: SHP674 | Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) | Seroconversion upon tretament | 2 Participants |
Secondary
Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2)
Time frame: Predose and 25 days post dose (Part 1 and part 2)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: SHP674 | Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) | Pre-existing Anti-PEG positive | 0 Participants |
| Part 1: SHP674 | Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) | Seroconversion upon treatment | 0 Participants |
| Part 2: SHP674 | Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) | Pre-existing Anti-PEG positive | 2 Participants |
| Part 2: SHP674 | Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) | Seroconversion upon treatment | 0 Participants |
Secondary
Survival Rate at 1 Year After the Start of Study Treatment
Survival rate is defined as the percentage of subjects who survived at 1 year after the start of study treatment.
Time frame: 1 year after the start of study treatment (from first dose up to 12 months)
Population: The analysis was performed on the safety set analysis, defined as the set of all subjects who had received at least one dose of SHP674 in Part 1 or Part 2 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: SHP674 | Survival Rate at 1 Year After the Start of Study Treatment | 3 Participants |
| Part 2: SHP674 | Survival Rate at 1 Year After the Start of Study Treatment | 23 Participants |