CAT-8015 in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

Adverse events that were suspected of a relationship to moxetumomab pasudotox and were greater than or equal to (>=) Grade 3 in severity were considered DLTs with the following additional criteria or exceptions: Participants with hematologic abnormalities of any grade, Grade 2 allergic reactions of bronchospasm or urticaria, or any Grade ≥ 3 allergic reaction, in the presence of premedication.

An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of investigational product and 30 days after the last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.

Vital signs included parameters as heart rate, blood pressure, temperature, weight, pulse oximetry and respiratory rate. TEAEs were events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug.

An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent were events between first dose of study drug and 30 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with grade 3 or higher treatment-emergent adverse events (5% cut off) for laboratory abnormalities were reported as clinically relevant laboratory changes.

An abnormal chemistry finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent were events between first dose of study drug and 30 days after the last dose that were absent before treatment or that worsened relative to pretreatment state.

Ophthalmologic examination included evaluation of retinal, corneal and lens abnormalities at baseline and end of treatment that were not present at screening. Participants who experienced abnormalitities during ophthalmologic examination recorded and reported.

Number of participants with abnormal ECG changes (compared with baseline) as assessed by study cardiologist

The 12-lead ECG data were summarized and evaluated for the following parameters: ,QT, QTC intervals and ventricular rate. Change from baseline in these parameters were reported.

Antitumor activity was assessed by best overall tumor response.

Objective response based on assessment of confirmed composite complete response (CRc) or partial response (PR) according to disease specific criteria [modified criteria for response in acute lymphoblastic leukemia (ALL)].

Relapse is defined as progressive disease (PD) following complete response (CR). Rate of relapse was only calculated for the subgroup of participants with complete response.

Time to disease response was measured from the start of moxetumomab pasudotox administration to the first documentation of response (CR or PR) and was assessed in participants who achieved objective response.

Duration of response was defined as the duration from the first documentation of objective response to the first documented disease progression.

Time to disease progression was measured from the start of treatment with moxetumomab pasudotox until the documentation of disease progression. Number of progressions were reported here.

Progression-free survival was measured from the start of treatment with moxetumomab pasudotox until the documentation of disease progression or death due to any cause, whichever occurs first. Number of progressions/deaths were reported here.

Overall survival was determined as the time from the start of treatment with Moxetumomab Pasudotox until death. Number of deaths were reported here.

The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.

The AUC (0 to infinity) is the area under the plasma concentration-time curve from time zero to infinity hours.

The 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 zone to infinite time (AUC[0-infinity]).

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Participants tested for immunogenicity to CAT-8015 (moxetumomab pasudotox) prior to enrollment, before each cycle and at end of study. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of moxetumomab pasudotox to its target, cluster of differentiation 22 (CD22), coated onto enzyme linked immunosorbent assay (ELISA) plates. It was used as a direct surrogate for biological activity based on the mechanism of action of this drug. Significant level of neutralizing antibody activity defined as the capacity of test plasma to inhibit greater than (>)50 percentage (%) of the binding of CAT-8015 to CD22 using an ELISA-based method.

Participants malignant cells (peripheral blood) was tested for cluster of differentiation 22 (CD22) expression by fluorescence-activated cell sorter (FACS) analysis.

Potential biomarkers include orthostatic blood pressure, albumin levels, weight change, edema and hypoxia were evaluated.