Clinical trial NCT02190721: A Study to Evaluate 5 μg/kg Tbo-filgrastim in Infants, Children and Adolescents With Solid Tumors Without Bone Marrow Involvement
Official title: A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Efficacy, and Immunogenicity of Daily Subcutaneous Administration of 5 ?g/kg Tbo-filgrastim in Infants, Children and Adolescents With Solid Tumors Without Bone Marrow Involvement
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neutropenia
Keywords: Neutropenia
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2014-07-15
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of daily subcutaneous administration of 5 μg/kg tbo-filgrastim in infants, children and adolescents with solid tumors without bone marrow involvement.


Eligibility criteria: Inclusion:

1. Male or female infants, children and adolescents aged 1 month to \<16 years.
2. Patients with solid tumors without bone marrow involvement, who are scheduled to receive myelosuppressive CTX.
3. Body weight ≥5 kg.
4. Patients must have an initial diagnosis and histologic proof of their malignancy. All enrolled subjects should have signed consent for a CTX regimen that is known to be myelotoxic, with counts expected to drop below the absolute neutrophil count (ANC) of 0.5 × 109/L for at least 3 days. These regimens would include at least one of the following:

   * Etoposide
   * doxorubicin
   * ifosfamide
   * cyclophosphamide
5. ANC and platelet count: Patients must have an ANC \>1 × 109/L and a platelet count \>100 × 109/L to be eligible for therapy at the start of CTX.
6. Normal cardiac, renal, and hepatic function.
7. All subjects must have a life expectancy of 12 weeks or more.
8. Performance Status: Lansky performance score \>60 (age 1 to \<16 years).

   * More criteria may apply, please contact the investigator for more information.

Exclusion:

1. Bone marrow involvement.
2. Active myelogenous leukemia or history of myelogenous leukemia.
3. Previous treatment with colony-stimulating factors (granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor, interleukin 11 \[IL-11\]) less than 6 weeks prior to study entry.
4. History of congenital neutropenia or cyclic neutropenia.
5. Pregnant or nursing female patients.
6. Fertile patients who do not agree to use highly reliable contraceptive measures Prior bone marrow or stem cell transplant, or prior radiation to ≥25% of bone marrow within the 4 weeks prior to the first tbo-filgrastim dose.
7. Ongoing active infection or history of infectious disease within 2 weeks prior to the screening visit.
8. Treatment with lithium at screening or planned during the study

   * More criteria may apply, please contact the investigator for more information.

Primary outcomes:
measure: Participants With Adverse Events (AEs)
timeFrame: Non-TEAE: signing of informed consent to Day -1 (last day of CTX in week 1). And > 30 days after last dose of tbo-filgrastim (Day 46+). TEAE timeframe: Day 1 (start of tbo-filgrastim) to <= 30 days after the last dose (up to Day 45)
measure: Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
timeFrame: Day 1 (start of tbo-filgrastim administration) up to Day 21
measure: Participants With Potentially Clinically Significant Abnormal Hematology Results
timeFrame: Day 1 (start of tbo-filgrastim administration) up to Day 21
measure: Participants With Potentially Clinically Significant Abnormal Vital Signs
timeFrame: Day 1 (start of tbo-filgrastim administration) up to Day 21
measure: Participants With Potentially Clinically Significant Abnormal Electrocardiogram Results
timeFrame: Day 1 (start of tbo-filgrastim administration) pre-dose, 4 hours post dose and 6 hours post dose; Day 21 (end of study visit)
measure: Participants With Negative Shifts From Baseline to End of Study in Physical Exam Findings
timeFrame: Baseline: Day -21, Day 21 (end of study visit)
measure: Participants With Injection Site Reactions to Tbo-Filgrastim Administration
timeFrame: Day 1 (start of tbo-filgrastim administration) up to Day 14
measure: Participants With Negative Shifts From Baseline to End of Study in Spleen Sonography Findings
timeFrame: Baseline: Day -21, Day 21 (end of study visit)
measure: Participants Who Were Alive at the 90 Day Follow-Up
timeFrame: 90 days post end of study visit (111 days from start of tbo-filgrastim administration)
Secondary outcomes:
measure: Participants With Positive Immunogenicity Findings Tested at Four Study Timepoints
timeFrame: Baseline (Day -21), Day 21 (end of study visit), Day 51 (30 Day follow-up) and Day 111 (90 Day follow-up)
measure: Maximum Observed Serum Concentration (Cmax) of Tbo-Filgrastim
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Time to Maximum Observed Serum Concentration (Tmax) of Tbo-Filgrastim
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Area Under The Serum Concentration-Time Curve From Time 0 To Time Of Last Quantifiable Concentration (AUClast)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Area Under The Serum Concentration-Time Curve From Time 0 To 12 Hours Postdose (AUC0-12)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: AUC From Time 0 to Infinity (AUC0-inf)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Elimination Half-life (t1/2)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Apparent Clearance (CL/F)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose of Day 1
measure: Apparent Volume of Distribution During the Terminal Phase (Vz/F)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Percentage of the AUC0-∞ That Is Due To the Extrapolation (%AUCext)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Terminal Elimination Rate (Lambda-z)
timeFrame: Within 1 hour before the tbo-filgrastim dose and at 2, 4, 6, 8, and 12 hours after the tbo-filgrastim dose on Day 1
measure: Participants With Severe Neutropenia
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Duration of Severe Neutropenia
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Area Under The Serum Drug Concentration By Time Curve Of Absolute Neutrophil Count (AUC ANC)
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Absolute Neutrophil Count (ANC) Nadir
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Tbo-filgrastim Administration
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to Absolute Neutrophil Count (ANC) Nadir From Beginning of Chemotherapy
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to ANC Recovery To ≥1.0 * 10^9/L From ANC Nadir
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to ANC Recovery To ≥2.0 * 10^9/L From ANC Nadir
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Tbo-filgrastim Administration
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Tbo-filgrastim Administration
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to ANC Recovery To ≥1.0 * 10^9/L From Start of Chemotherapy
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Time to ANC Recovery To ≥2.0 * 10^9/L From Start of Chemotherapy
timeFrame: ANC blood samples collected within 1 hour before the tbo-filgrastim dose on Day 1, and on Days 5, 6, 7, 10, 12, 15 and at the end of study visit (up to Day 21)
measure: Participants With Febrile Neutropenia During the First Cycle of Chemotherapy
timeFrame: (relative to tbo-filgrastim therapy) Days -7 to Day 14
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Teva Investigational Site 12958
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 12951
state: California
city: Jackson
country: United States
facility: Teva Investigational Site 12954
state: Mississippi
city: Las Vegas
country: United States
facility: Teva Investigational Site 12953
state: Nevada
city: Valhalla
country: United States
facility: Teva Investigational Site 12959
state: New York
city: Columbus
country: United States
facility: Teva Investigational Site 12960
state: Ohio
city: Houston
country: United States
facility: Teva Investigational Site 12957
state: Texas
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59104
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59105
city: Rijeka
country: Croatia
facility: Teva Investigational Site 60015
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60014
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60016
city: Budapest
country: Hungary
facility: Teva Investigational Site 51186
city: Budapest
country: Hungary
facility: Teva Investigational Site 51185
city: Szeged
country: Hungary
facility: Teva Investigational Site 51184
city: Gdansk
country: Poland
facility: Teva Investigational Site 53249
city: Lublin
country: Poland
facility: Teva Investigational Site 53248
city: Warszawa
country: Poland
facility: Teva Investigational Site 53245
city: Warszawa
country: Poland
facility: Teva Investigational Site 53246
city: Wroclaw
country: Poland
facility: Teva Investigational Site 53247
city: Bucharest
country: Romania
facility: Teva Investigational Site 52063
city: Cluj-Napoca, Cluj
country: Romania
facility: Teva Investigational Site 52064
city: Timisoara
country: Romania
facility: Teva Investigational Site 52065
city: Chelyabinsk
country: Russian Federation
facility: Teva Investigational Site 50282
city: Krasnodar
country: Russian Federation
facility: Teva Investigational Site 50281
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50284
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 50280
city: Volgograd
country: Russian Federation
facility: Teva Investigational Site 50283
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 58147
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58145
city: Lviv
country: Ukraine
facility: Teva Investigational Site 58148
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 58146
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 58149
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: