Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Immunotoxin HA22

Immunotoxins

Immunoconjugates

Immunologic Factors

Participants received intravenous infusion of 5 mcg/kg moxetumomab pasudotox (CAT-8015) without concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 10 mcg/kg moxetumomab pasudotox (CAT-8015) without concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 20 mcg/kg moxetumomab pasudotox (CAT-8015) without concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 20 mcg/kg moxetumomab pasudotox (CAT-8015) with concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 30 mcg/kg moxetumomab pasudotox (CAT-8015) without concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 30 mcg/kg moxetumomab pasudotox (CAT-8015) with concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 40 mcg/kg moxetumomab pasudotox (CAT-8015) with concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 32 mcg/kg moxetumomab pasudotox (CAT-8015) of process 3 material every other day (QoD) in a 21-day cycle for a total of 10 doses per cycle.

Participants received intravenous infusion of 50 mcg/kg moxetumomab pasudotox (CAT-8015) without concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

Participants received intravenous infusion of 50 mcg/kg moxetumomab pasudotox (CAT-8015) continuous every other day (QoD) in a 21-day cycle for a total of 10 doses per cycle.

CAT-8015 (Moxetumomab Pasudotox)

Medimmune LLC Medimmune LLC

A dose-escalation study to estimate maximum cummulative dose (MTCD) of CAT-8015 that can be safely administered to a participant.

A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Children, Adolescents and Young Adults with Refractory CD22+ Acute Lymphoblastic Leukemia (ALL) or Non-Hodgkin Lymphoma (NHL) to estimate the maximum tolerated cummulative dose (MTCD), defined as the highest dose and number of doses that can be safely administered to a participant, and to establish a safe dose, based on the MTCD, for subsequent clinical testing.

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

A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Children, Adolescents and Young Adults With Refractory CD22+ Acute Lymphoblastic Leukemia (ALL) or Non-Hodgkin Lymphoma (NHL)

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.

National Cancer Institute (NCI)

MedImmune LLC

5 UG/KG SCHEMA A

10 UG/KG SCHEMA A

20 UG/KG SCHEMA A

20 UG/KG SCHEMA B

30 UG/KG SCHEMA A

30 UG/KG SCHEMA B

40 UG/KG SCHEMA B

32 UG/KG SCHEMA C

50 UG/KG SCHEMA B

50 UG/KG SCHEMA C

5 Microgram Per Kilogram (mcg/kg)

10 Microgram Per Kilogram (mcg/kg)

20 Microgram Per Kilogram (mcg/kg): Schema A

20 Microgram Per Kilogram (mcg/kg): Schema B

30 Microgram Per Kilogram (mcg/kg): Schema A

30 Microgram Per Kilogram (mcg/kg): Schema B

40 Microgram Per Kilogram (mcg/kg): Schema B

32 Microgram Per Kilogram (mcg/kg): Schema C

50 Microgram Per Kilogram (mcg/kg): Schema B

50 Microgram Per Kilogram (mcg/kg): Schema C

Total

Age, Continuous

Sex: Female, Male

Safety Population includes all participants who received any treatment of study drug.

Mark Lanasa, MD Associate Director, Clinical Development, Oncology

Evaluable Population for DLT included all participants who received any treatment of moxetumomab pasudotox (CAT-8015) and completed the DLT period without a DLT, or did not complete the DLT period due to a DLT. Here, "N" is number of participants evaluated for this outcome measure.

Number of Participants With Dose Limiting Toxicities (DLTs)

TEAEs

TESAEs

Safety Population included all participants who received any treatment of study drug.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Tachycardia

Arrhythmia

Bradycardia

Sinus bradycardia

Sinus tachycardia

Pyrexia

Dyspnoea

Respiratory distress

Tachypnoea

Hypertension

Hypotension

Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)

Febrile neutropenia

Anemia

Leukopenia

Lymphopenia

Neutropenia

Thrombocytopenia

Safety population included all participants who received any treatment of study drug.

Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)

Alanine aminotransferase increased

Aspartate aminotransferase increased

Blood creatinine increased

Blood lactate dehydrogenase increased

Blood urea increased

Hyperglycaemia

Hyperphosphataemia

Hypoalbuminaemia

Hypocalcaemia

Hypokalaemia

Hypomagnesaemia

Hyponatraemia

Hypophosphataemia

Treatment-Emergent Adverse Events (TEAEs) Related to Chemistry Abnormalities Occurring in Greater Than (>) 5 Percent of Participants

Number of Participants With Abnormalities in Ophthalmologic Examination at End of Treatment That Were Not Present at Baseline

Number of Participants With Change From Baseline in Normal Sinus Rhythm Findings in ECG

QT interval

QTC interval

Ventricluar rate

Change From Baseline to End of Treatment in Clinical Findings in Electrocardiogram (ECG) QT, QTC Interval and Ventricular Rate

Composite complete response

Complete response

complete response with incomplete count recovery

Partial response

Hematological activity

Stable disease

Progressive disease

Evaluable Population for Efficacy included all participants who received any treatment of moxetumomab pasudotox and had at least 1 disease assessment after the initiation of moxetumomab pasudotox. Here, "N" is number of participants analyzed for this outcome measure.

Best Overall Tumor Response

Efficacy population included all participants who received any treatment of study drug and had at least 1 disease assessment after the initiation of study drug. Here, "N" is number of participants analyzed for this outcome measure.

Objective Response Rate (ORR)

Efficacy population. Here, "N" is number of participants with CR in the respective cohort. Rate of relapse could not be estimated as none of the participants experienced CR in the 5 mcg/kg, 20 mcg/kg (Schema A) and 30 mcg/kg (schema A) cohort of the study.

Percentage of Participants With Relapse of Disease

Evaluable Population for Efficacy. Here, "N" is number of participants with objective disease response in the respective cohort. Time to disease response could not be estimated as none of the participants experienced OR in the 5 mcg/kg, 20 mcg/kg (schema A) and 30 mcg/kg (schema A).

Time to Disease Response

Evaluable Population for Efficacy. Here, "N" is number of participants with objective disease response in the respective cohort. DR could not be estimated as none of the participants experienced OR in the 5 mcg/kg, 20 mcg/kg (schema A) and 30 mcg/kg (schema A).

Duration of Response (DR)

Time to Disease Progression (TDP)

Progression-Free Survival (PFS)

Overall Survival (OS)

Participants received intravenous infusion of 20 mcg/kg CAT-8015 with/without concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

20 Microgram Per Kilogram (mcg/kg)

Participants received intravenous infusion of 30 mcg/kg CAT-8015 with/without concomitant corticosteroid administration every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

30 Microgram Per Kilogram (mcg/kg)

Participants received intravenous infusion of 50 mcg/kg CAT-8015 without concomitant corticosteroid administration/continuous every other day (QoD) in a 21-day cycle for a total of 6 doses per cycle.

50 Microgram Per Kilogram (mcg/kg)

Evaluable Population for efficacy included all participants who received any treatment of study drug and had at least 1 disease assessment after the initiation of study drug.

Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox

Evaluable Population for Efficacy included all participants who received any treatment of study drug and had at least 1 disease assessment after the initiation of study drug.

Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUC [0 to Infinity]) for Moxetumomab Pasudotox

Systemic Clearance (CL) for Moxetumomab Pasudotox

Terminal Phase Elimination Half Life (t1/2) for Moxetumomab Pasudotox

ADA present by screening assay

Neutralizing ADA present by functional assay

Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody

Composite complete response(n=0,1,0,1,0,1,0,2,2,3)

Complete response (n=0,1,0,1,0,1,0,2,2,3)

Partial response (n=0,0,0,0,0,1,0,1,0,2)

Hematological activity (n=0,0,0,2,3,0,3,1,1,2)

Stable response (n=0,0,1,1,1,1,2,1,0,4)

Progressive disease (n=1,0,0,0,0,1,1,2,3,1)

Safety population included all participants who received any treatment of study drug. Here, n = participants evaluable for specified category for each arm, respectively

Spots Global Cancer Trial Database for CAT-8015 in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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