Trial Outcomes & Findings for Study in Pediatrics With Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma (NCT NCT02227108)

NCT ID: NCT02227108

Last Updated: 2017-04-06

Results Overview

The CRc is defined as achieving complete response (CR), or CR with incomplete count recovery \[CRi\]) in participants with relapsed or refractory B-cell ALL or B-cell lymphoblastic lymphoma. Complete response (CR) as per International Working Group (IWG) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Morphologic CR with incomplete blood count recovery (CRi) is defined as the above CR criteria without specified blood counts. The efficacy assessments were evaluated as per investigator assessment.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Results posted on

2017-04-06

Participant Flow

A total of 37 participants were screened, of which 5 did not meet eligibility criteria and were considered as screen failures; the remaining 32 participants entered into the study and 30 participants were treated with moxetumomab pasudotox.

Participant milestones

Participant milestones
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Overall Study
STARTED
32
Overall Study
Treated
30
Overall Study
COMPLETED
1
Overall Study
NOT COMPLETED
31

Reasons for withdrawal

Reasons for withdrawal
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Overall Study
Did not receive treatment
2
Overall Study
Other
3
Overall Study
Progressive disease
17
Overall Study
Initiation of alternative therapy
2
Overall Study
Investigator discretion
1
Overall Study
Adverse Event
6

Baseline Characteristics

Study in Pediatrics With Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=32 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Age, Continuous
10.5 Years
STANDARD_DEVIATION 3.9 • n=39 Participants
Sex: Female, Male
Female
13 Participants
n=39 Participants
Sex: Female, Male
Male
19 Participants
n=39 Participants

PRIMARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

The CRc is defined as achieving complete response (CR), or CR with incomplete count recovery \[CRi\]) in participants with relapsed or refractory B-cell ALL or B-cell lymphoblastic lymphoma. Complete response (CR) as per International Working Group (IWG) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Morphologic CR with incomplete blood count recovery (CRi) is defined as the above CR criteria without specified blood counts. The efficacy assessments were evaluated as per investigator assessment.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Percentage of Participants With Composite Complete Response (CRc)
10.7 percentage of participants
Interval 2.3 to 28.2

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

The MRD-negative CRc rate was defined as the percentage of participants who achieved CRc and became MRD-negative as determined by flow cytometry performed by a central analysis laboratory. The CRc is defined as complete response (CR), or complete response with incomplete count recovery (CRi). Complete response (CR) as per International Working Group (IWG) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Morphologic CR with incomplete blood count recovery (CRi) is defined as the above CR criteria without specified blood counts.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Percentage of Participants With Minimal Residual Disease (MRD)-Negative CRc Rate
0 percentage of participants

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

The ORR, defined as the percentage of participants with CRc or partial response (PR), was estimated; the Clopper Pearson (Exact) 95% CI was calculated. The CRc is defined as complete response (CR), or complete response with incomplete count recovery (CRi). Complete response (CR) as per International Working Group (IWG) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Morphologic CR with incomplete blood count recovery (CRi) is defined as the above CR criteria without specified blood counts.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Overall Response Rate (ORR)
28.6 percentage of participants
Interval 13.2 to 48.7

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

Time to overall response was evaluated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Time to Overall Response
0.66 months
Interval 0.53 to 0.76

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number and percentage of participants for the following categories: CRc, PR, HA, SD, PD, and not evaluable. Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma. Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes and in size of liver or spleen. Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Best Overall Response (BOR)
Composite complete response
10.7 percentage of participants
Best Overall Response (BOR)
Partial response
17.9 percentage of participants
Best Overall Response (BOR)
Hematological activity
7.1 percentage of participants
Best Overall Response (BOR)
Stable disease
21.4 percentage of participants
Best Overall Response (BOR)
Progressive disease
39.3 percentage of participants
Best Overall Response (BOR)
No evaluation available
3.6 percentage of participants

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: The intent to treat (ITT) population included all participants who entered the study. Here, number of participants analysed, "N" included evaluable participants for this outcome measure.

Change in bone marrow blast percentage from baseline was evaluated. If the percentage (%) blasts (at least 200 cells counted) is less than (\<) 5%, it is considered as M1, 5 to 25% considered as M2, greater than (\>) 25% considered as M3. Stages with the higher blasts relate to worse outcomes.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=26 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Bone Marrow Blast Percentage Change
Baseline M1, post-baseline M1
0 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M1, post-baseline M2
0 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M1, post-baseline M3
3.8 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M2, post-baseline M1
0 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M2, post-baseline M2
0 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M2, post-baseline M3
7.7 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M3 post-baseline M1
3.8 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M3 post-baseline M2
11.5 percentage of participants
Bone Marrow Blast Percentage Change
Baseline M3 post-baseline M3
73.1 percentage of participants

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

The percentage of participants who became eligible for SCT after treatment with moxetumomab pasudotox were provided. The Clopper Pearson (Exact) 95% CI was calculated.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Percentage of Participants Who Became Eligible to Receive an Stem Cell Transplant (SCT) After Treatment With Moxetumomab Pasudotox
0 percentage of participants

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy population included participants who received moxetumomab pasudotox, completed a baseline disease assessment and had at least one post-baseline assessment. Since study was terminated prematurely, no participant received SCT after treatment with moxetumomab pasudotox, hence data were not collected for this Outcome measure.

The time to SCT was defined as the duration from the start of treatment with moxetumomab pasudotox until the date when the subject became eligible for SCT. The time to SCT was to be summarized using the Kaplan-Meier method, and was only to be evaluated for the subgroup of subjects who became eligible for SCT after treatment with moxetumomab pasudotox.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

The percentage of participants who were neutropenic at study entry and experienced HA after treatment with moxetumomab pasudotox was evaluated. The Clopper Pearson (Exact) 95% CI was calculated.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Percentage of Participants Who Were Neutropenic at Study Entry and Who Experienced Hematologic Activity (HA)
3.6 percentage of participants

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment. Here, number of participants analysed, "N" included evaluable participants for this outcome measure.

DOCR was defined as the duration from the first documentation of CRc to the first documented disease progression.The CRc is defined as achieving complete response (CR), or CR with incomplete count recovery \[CRi\]) in participants with relapsed or refractory B-cell ALL or B-cell lymphoblastic lymphoma. Kaplan-Meier method was used for evaluation.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=1 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Duration of Complete Response (DOCR)
1.97 months
Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

DOR was to be defined as the duration from the first documentation of overall response to the first documented disease progression. Kaplan-Meier method was used for evaluation.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Duration of Overall Response (DOR)
0.95 months
Interval 0.59 to 1.97

SECONDARY outcome

Timeframe: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

PFS was measured from the start of treatment with moxetumomab pasudotox until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Progression-Free Survival (PFS)
1.4 months
Interval 0.3 to 8.4

SECONDARY outcome

Timeframe: Baseline to end of study or last contact date, up to 1 year

Population: Efficacy evaluable population included all participants who received any amount of moxetumomab pasudotox and completed a baseline disease assessment and had at least one post-baseline disease assessment.

OS was determined as the time from the start of treatment with moxetumomab pasudotox until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=28 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Overall Survival (OS)
3.6 months
Interval 0.4 to 9.8

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study drug, up to 1 year

Population: Safety population includes all participants who received any amount of moxetumomab pasudotox.

Treatment-emergent adverse events (TEAEs), were defined as events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=30 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
TEAEs
30 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
TESAEs
16 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study drug, up to 1 year

Population: Safety population includes all participants who received any amount of moxetumomab pasudotox.

Laboratory tests were grouped according to hematology, serum chemistry, and urinalysis. Laboratory abnormalities with toxicity grades according to NCI CTCAE Version 4.03 were derived according to laboratory values and reported as treatment-emergent adverse events.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=30 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Anaemia
11 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Febrile neutropenia
7 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Haemolytic uraemic syndrome
4 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Thrombocytopenia
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Platelet count decreased
9 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Neutrophil count decreased
6 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
White blood cell count decreased
5 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Lymphocyte count decreased
2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
International normalised ratio increased
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Alanine aminotransferase increased
11 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Aspartate aminotransferase increased
8 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Gamma-glutamyltransferase increased
4 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Blood bilirubin increased
2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Blood creatinine increased
2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Blood lactate dehydrogenase increased
2 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Bilirubin conjugated
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Blood albumin decreased
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Blood urea increased
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Glucose tolerance increased
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hypoalbuminaemia
6 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hypocalcaemia
6 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hypokalaemia
5 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hyponatraemia
5 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hyperglycaemia
4 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hypophosphataemia
3 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hypermagnesaemia
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hypomagnesaemia
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Hepatic function abnormal
1 participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Proteinuria
1 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study drug, up to 1 year

Population: Safety population includes all participants who received any amount of moxetumomab pasudotox.

Participants were evaluated for ECG abnormalities.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=30 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
0 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after the last dose of study drug, up to 1 year

Population: Safety population includes all participants who received any amount of moxetumomab pasudotox.

Participants who experienced vital signs abnormalities recorded as TEAEs were reported.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=30 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Tachycardia
3 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Pyrexia
16 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Dyspnoea
6 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Hypoxia
4 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Hypertension
8 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Hypotension
4 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Weight decreased
1 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Weight increased
10 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Bradycardia
7 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Sinus bradycardia
1 participants
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Sinus tachycardia
3 participants

SECONDARY outcome

Timeframe: Prior to the Start of Each Cycle for Cycles 1, 2, 3, and Subsequent Odd-Numbered Cycles, End of Treatment, and 30 Day Follow-up Visit, up to 1 year

Population: Safety population includes all participants who received any amount of moxetumomab pasudotox. Here, number of participants analysed, "N" included participants with at least one post-baseline sample.

Immunogenicity assessment included determination of antidrug (moxetumomab pasudotox) antibodies and neutralizing antidrug antibodies in serum samples. Titers and specificity were determined for NAb-positive participants. Specificity were observed in participants who had ADAs directed to the PE38 domain of moxetumomab pasudotox and increase in titers were observed in participants who tested ADA-positive at baseline. Moxetumomab pasudotox ADA-titer is a validated immunoassay, which determines titers or levels of ADAs present in ADA-positive samples.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=23 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (NAb)
Anti-drug Antibody (ADA)
13 participants
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (NAb)
Neutralizing Antibodies (NAb)
13 participants
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (NAb)
Increase in Titers
3 participants
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (NAb)
Specificity
13 participants

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion of Day 1 of Cycle 1

Population: Safety population who provided at least one measurable Pharmacokinetic concentration. Here, number of participants analysed, "N" included evaluable participants for this outcome measure.

AUC (0-infinity) = Area under the serum concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (tinfinity). It was calculated by extrapolating the concentrationtime curve from time zero to infinity using the linear/log trapezoidal rule.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=7 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC0-inf) After the First Dose of Cycle 1
1200 hour*nanogram per milliliter (hr*ng/mL)
Standard Deviation 224

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1

Population: Safety population who provided at least one measurable Pharmacokinetic concentration. Here, number of participants analysed, "N" included evaluable participants for this outcome measure.

AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC0-t is defined as AUC from time zero to the last data point above the lower limit of quantification.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=21 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Area Under the Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC0-last] After the First Dose of Cycle 1
794 hour*nanogram per milliliter (hr*ng/mL)
Standard Deviation 239

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1

Population: Safety population who provided at least one measurable Pharmacokinetic concentration.

Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=26 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Maximum Observed Drug Concentration in Plasma (Cmax) After the First Dose of Cycle 1
457 nanogram per milliliter
Standard Deviation 128

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1

Population: Safety population who provided at least one measurable Pharmacokinetic concentration.

Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=26 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Time to Reach Maximum Drug Concentration in Plasma (Tmax) After the First Dose of Cycle 1
0.54 hour
Standard Deviation 0.05 • Interval 0.5 to 0.75

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1

Population: Safety population who provided at least one measurable Pharmacokinetic concentration. Here, number of participants analysed, "N" included evaluable participants for this outcome measure.

Terminal phase elimination half-life is the time measured for the serum/plasma concentration to decrease by one half, calculated as natural logarithmic (log)-transformed (ln) value of 2 divided by elimination rate constant (lambda); that is \[ln(2)/lambda\]. Elimination rate constant (lambda) was estimated via linear regression of the time versus log concentration.

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=7 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Terminal Phase Elimination Half Life (t1/2) After the First Dose of Cycle 1
1.02 hour
Full Range 0.213 • Interval 0.82 to 1.44

SECONDARY outcome

Timeframe: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1

Population: Safety population who provided at least one measurable Pharmacokinetic concentration. Here, number of participants analysed, "N" included evaluable participants for this outcome measure.

CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC\[0-infinity\]).

Outcome measures

Outcome measures
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=7 Participants
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Systemic Clearance (CL) After the First Dose of Cycle 1
34.4 milliliter per hour per kilogram
Full Range 5.72 • Interval 24.4 to 41.8

Adverse Events

Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)

Serious events: 16 serious events
Other events: 30 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=30 participants at risk
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Blood and lymphatic system disorders
Febrile neutropenia
10.0%
3/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Blood and lymphatic system disorders
Haemolytic uraemic syndrome
13.3%
4/30 • Number of events 4 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Eye disorders
Vision blurred
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
General disorders
Fatigue
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
General disorders
Pyrexia
13.3%
4/30 • Number of events 4 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Infections and infestations
Device related infection
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Infections and infestations
Infection
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Infections and infestations
Septic shock
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Infections and infestations
Staphylococcal sepsis
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Platelet count decreased
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Bone pain
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Nervous system disorders
Encephalopathy
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Nervous system disorders
Headache
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Nervous system disorders
Somnolence
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Psychiatric disorders
Anxiety
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Respiratory, thoracic and mediastinal disorders
Respiratory distress
3.3%
1/30 • Number of events 1 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Vascular disorders
Capillary leak syndrome
16.7%
5/30 • Number of events 5 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose

Other adverse events

Other adverse events
Measure
Moxetumomab Pasudotox 40 Microgram Per Kilogram (mcg/kg)
n=30 participants at risk
Participants received 6 doses of moxetumomab pasudotox 40 mcg/kg intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Blood and lymphatic system disorders
Anaemia
36.7%
11/30 • Number of events 29 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Blood and lymphatic system disorders
Febrile neutropenia
13.3%
4/30 • Number of events 13 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Cardiac disorders
Sinus tachycardia
10.0%
3/30 • Number of events 6 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Cardiac disorders
Tachycardia
10.0%
3/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Eye disorders
Periorbital oedema
10.0%
3/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Eye disorders
Vision blurred
16.7%
5/30 • Number of events 6 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Gastrointestinal disorders
Abdominal pain
10.0%
3/30 • Number of events 5 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Gastrointestinal disorders
Constipation
13.3%
4/30 • Number of events 5 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Gastrointestinal disorders
Diarrhoea
10.0%
3/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Gastrointestinal disorders
Nausea
26.7%
8/30 • Number of events 10 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Gastrointestinal disorders
Vomiting
13.3%
4/30 • Number of events 4 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
General disorders
Face oedema
13.3%
4/30 • Number of events 5 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
General disorders
Fatigue
6.7%
2/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
General disorders
Oedema peripheral
16.7%
5/30 • Number of events 8 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
General disorders
Pyrexia
40.0%
12/30 • Number of events 40 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Infections and infestations
Pneumonia
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Alanine aminotransferase increased
36.7%
11/30 • Number of events 45 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Aspartate aminotransferase increased
26.7%
8/30 • Number of events 34 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Blood bilirubin increased
6.7%
2/30 • Number of events 4 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Blood creatinine increased
6.7%
2/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Blood lactate dehydrogenase increased
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Gamma-glutamyltransferase increased
13.3%
4/30 • Number of events 18 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Lymphocyte count decreased
6.7%
2/30 • Number of events 4 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Neutrophil count decreased
20.0%
6/30 • Number of events 21 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Platelet count decreased
26.7%
8/30 • Number of events 59 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
Weight increased
33.3%
10/30 • Number of events 21 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Investigations
White blood cell count decreased
16.7%
5/30 • Number of events 24 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Metabolism and nutrition disorders
Hyperglycaemia
13.3%
4/30 • Number of events 12 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Metabolism and nutrition disorders
Hypoalbuminaemia
20.0%
6/30 • Number of events 11 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Metabolism and nutrition disorders
Hypocalcaemia
20.0%
6/30 • Number of events 28 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Metabolism and nutrition disorders
Hypokalaemia
16.7%
5/30 • Number of events 27 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Metabolism and nutrition disorders
Hyponatraemia
16.7%
5/30 • Number of events 12 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Metabolism and nutrition disorders
Hypophosphataemia
10.0%
3/30 • Number of events 13 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Back pain
20.0%
6/30 • Number of events 6 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Bone pain
10.0%
3/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Groin pain
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Myalgia
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Neck pain
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Pain in extremity
20.0%
6/30 • Number of events 6 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Musculoskeletal and connective tissue disorders
Pain in jaw
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Nervous system disorders
Headache
40.0%
12/30 • Number of events 22 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Nervous system disorders
Paraesthesia
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Psychiatric disorders
Anxiety
10.0%
3/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Respiratory, thoracic and mediastinal disorders
Cough
10.0%
3/30 • Number of events 3 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Respiratory, thoracic and mediastinal disorders
Dyspnoea
20.0%
6/30 • Number of events 9 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Respiratory, thoracic and mediastinal disorders
Epistaxis
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Respiratory, thoracic and mediastinal disorders
Hypoxia
13.3%
4/30 • Number of events 6 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Respiratory, thoracic and mediastinal disorders
Wheezing
6.7%
2/30 • Number of events 2 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Vascular disorders
Hypertension
26.7%
8/30 • Number of events 12 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose
Vascular disorders
Hypotension
13.3%
4/30 • Number of events 4 • The period immediately following the time that written informed consent is obtained through Day 30 after the last dose

Additional Information

AstraZeneca Clinical Study Information Center

MedImmune LLC

Phone: 1-877-240-9479

Results disclosure agreements

  • Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
  • Publication restrictions are in place

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