Clinical trial NCT00659425: CAT-8015 in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma
Keywords: Moxetumomab pasudotox
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-04-16
Enrollment: 57
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

- Histologically confirmed diagnosis of acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma; - Measurable or evaluable disease. - Evidence of CD22-positive malignancy by one of the following criteria: - greater than or equal to (\>=) 30 % of malignant cells from a disease site cluster of differentiation 22+ (CD22+) by fluorescence-activated cell sorter (FACS) analysis or; ≥ 15 % of malignant cells from a disease site CD22+ by immunohistochemistry (IHC). Stage of disease: - Participants must have relapsed or refractory disease and have received at least one standard chemotherapy and one salvage regimen or allogeneic stem cell transplant; - Relapse after prior autologous or allogeneic HSCT is allowed. In the event of relapse after prior allogeneic HSCT, the participant must be at least 100 days post-transplant and have no evidence of ongoing active graft-vs-host disease; - Recovered from the acute toxic effects of all prior therapy before entry. Performance status: - Participants greater than or equal to (\>=) 12 years of age: Eastern Cooperative Oncology Group (ECOG) score of 0, 1, 2, or 3; - Participants \< 12 years of age: Lansky scale \>= 50%; - Participants who are unable to walk because of paralysis, but who are up in a wheel chair will be considered ambulatory for the purpose of calculating the performance score. Participants with the following central nervous system (CNS) status, are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy. - Female and male participants with childbearing potential and their sexual partners must agree to use an approved method of contraception during the study.

Exclusion Criteria:

- Participants meeting any of the following criteria are not eligible for participation in the study: - Isolated testicular or CNS ALL; Hepatic function: - Inadequate liver function defined as total bilirubin \> 2 × upper limit of normal (ULN) (except in the case of participants with documented Gilbert's disease \> 5 × ULN) or transaminases (ALT and aspartate aminotransferase \[AST\]) \> 5 × ULN based on age- and laboratory-specific normal ranges; Renal function: - With greater than age-adjusted normal serum creatinine (see Table below) and a creatinine clearance \> 60 millilitre per minute mL/min/1.73 m2. - Age(Years)- Maximum Serum Creatinine (mg/dl)\[≤5,0.8\] \[5 \< age less than or equal to 10,1.0\] \[10 \< age less than or equal to 15,1.2 \[\> 15, 1.5\] Hematologic function: - For non-leukemic subjects only, absolute neutrophil count (ANC) \< 1000/cmm, or platelet count \< 50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (ie potentially reversible with anti-neoplastic therapy); - Participants with CNS 3 disease; - Hyperleukocytosis (≥ 50,000 blasts/µL) or rapidly progressive disease (PD) that in the estimation of the investigator and sponsor would compromise ability to complete study therapy; - Prior treatment with CAT-3888 (BL22) or any pseudomonas-exotoxin-containing compound; - HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs); - Active hepatitis B or C infection.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 up to 21 days of Cycle 1 (each cycle duration was of 21 days)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study drug administration until 30 days after the last dose of study drug
measure: Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration until 30 days after the last dose of study drug
measure: Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to 30 days after the last dose of study drug
measure: Treatment-Emergent Adverse Events (TEAEs) Related to Chemistry Abnormalities Occurring in Greater Than (>) 5 Percent of Participants
timeFrame: From start of study drug administration up to 30 days after the last dose of study drug
measure: Number of Participants With Abnormalities in Ophthalmologic Examination at End of Treatment That Were Not Present at Baseline
timeFrame: Baseline and end of treatment (up to 1 year after the last participants begins study drug treatment)
measure: Number of Participants With Change From Baseline in Normal Sinus Rhythm Findings in ECG
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Change From Baseline to End of Treatment in Clinical Findings in Electrocardiogram (ECG) QT, QTC Interval and Ventricular Rate
timeFrame: Baseline and end of treatment (up to 1 year after the last participants begins study drug treatment)
measure: Best Overall Tumor Response
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Objective Response Rate (ORR)
timeFrame: Baseline until end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Percentage of Participants With Relapse of Disease
timeFrame: Baseline until end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Time to Disease Response
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Duration of Response (DR)
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment
measure: Time to Disease Progression (TDP)
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment
measure: Progression-Free Survival (PFS)
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Overall Survival (OS)
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox
timeFrame: Cycles 1, 2 and every 4th cycle: pre-dose, end of infusion (EOI), 1, 1.5, 2.5, 4 and 8 hours post-dose of Dose 1; pre-dose and end of infusion after Dose 6
measure: Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUC [0 to Infinity]) for Moxetumomab Pasudotox
timeFrame: Cycles 1, 2 and every 4th cycle: pre-dose, end of infusion (EOI), 1, 1.5, 2.5, 4 and 8 hours post-dose of Dose 1; pre-dose and end of infusion after Dose 6
measure: Systemic Clearance (CL) for Moxetumomab Pasudotox
timeFrame: Cycles 1, 2 and every 4th cycle: pre-dose, end of infusion (EOI), 1, 1.5, 2.5, 4 and 8 hours post-dose of Dose 1; pre-dose and end of infusion after Dose 6
measure: Terminal Phase Elimination Half Life (t1/2) for Moxetumomab Pasudotox
timeFrame: Cycles 1, 2 and every 4th cycle: pre-dose, end of infusion (EOI), 1, 1.5, 2.5, 4 and 8 hours post-dose of Dose 1; pre-dose and end of infusion after Dose 6
Secondary outcomes:
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody
timeFrame: Baseline until end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: CD22 Expression Cells in Peripheral Blood by Best Response
timeFrame: Baseline until end of treatment (up to 1 year after the last participant begins study drug treatment)
measure: Number of Participants With Potential Biomarkers of Predicting Capillary Leak Syndrome (CLS)
timeFrame: Baseline and end of treatment (up to 1 year after the last participant begins study drug treatment)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
affiliation: MedImmune LLC
name: Medimmune LLC Medimmune LLC
role: STUDY_DIRECTOR
References:
citation: Wayne AS, Shah NN, Bhojwani D, Silverman LB, Whitlock JA, Stetler-Stevenson M, et al. Pediatric phase 1 trial of moxetumomab pasudotox: activity in chemotherapy refractory acute lymphoblastic leukemia (ALL) . http://cancerres.aacrjournals.org/content/74/19_Supplement/CT230.short
citation: Wayne AS, Shah NN, Bhojwani D, Silverman LB, Whitlock JA, Stetler-Stevenson M, Sun W, Liang M, Yang J, Kreitman RJ, Lanasa MC, Pastan I. Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia. Blood. 2017 Oct 5;130(14):1620-1627. doi: 10.1182/blood-2017-02-749101. Epub 2017 Aug 9.