A Study to Evaluate 5 μg/kg Tbo-filgrastim in Infants, Children and Adolescents With Solid Tumors Without Bone Marrow Involvement

NCT02190721 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: XM02-ONC-2012014-001772-55
• Study Type: interventional
• Target: 50
• Locations: 8 countries
• Sites: 33

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.

Conditions

Neutropenia

Keywords

Neutropenia

Outcome Measures

Primary Outcomes (9)

• Participants With Adverse Events (AEs)

  An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A treatment-emergent AE (TEAE) is an AE occurring during the timeframe. A non-TEAE is any AE not considered a TEAE. Severity was rated by the investigator using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale where 3=severe but not life-threatening, 4=life-threatening and 5=death. Relation of AE to treatment was determined by the investigator (related=reasonable possibility). Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

  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)

• Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results

  Serum chemistry tests included alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, indirect bilirubin, total bilirubin, calcium, creatinine, gammaglutamyl transpeptidase (GGT), glucose, potassium, lactate dehydrogenase (LDH), phosphate, sodium and uric acid. Only tests with potentially clinically significant abnormal results are reported. ULN = upper limit of normal

  Day 1 (start of tbo-filgrastim administration) up to Day 21

• Participants With Potentially Clinically Significant Abnormal Hematology Results

  Hematology tests included Basophils ABS (x 10\^9/L), Basophils (%), Eosinophils ABS (x 10\^9/L), Eosinophils (%), Hematocrit (%), Hemoglobin (g/L), Lymphocytes Absolute Count (ABS) (x 10\^9/L), Lymphocytes (%), Monocytes ABS (x 10\^9/L), Monocytes (%), Neutrophils ABS (x 10\^9/L), Neutrophils (%), Platelets (x 10\^9/L), Red Blood Cell (RBC) (x 10\^12/L), White Blood Cell (WBC) (x 10\^9/L). Only tests with potentially clinically significant abnormal results are reported. ULN = upper limit of normal

  Day 1 (start of tbo-filgrastim administration) up to Day 21

• Participants With Potentially Clinically Significant Abnormal Vital Signs

  Vital sign tests included Pulse Rate (bpm), Systolic BP (mmHg), Diastolic BP (mmHg), Respiratory Rate (bpm), and Temperature (°C). Only tests with potentially clinically significant abnormal results are reported.

  Day 1 (start of tbo-filgrastim administration) up to Day 21

• Participants With Potentially Clinically Significant Abnormal Electrocardiogram Results

  Triplicate 12-lead ECGs were conducted at screening, predose, 4 and 6 hours postdose on day 1 of tbo-filgrastim administration, and at the end-of-study visit. The ECGs were interpreted by both the investigator and a qualified physician at the central diagnostic center as normal, abnormal not clinically significant, or abnormal clinically significant. The following parameters were measured/derived for each ECG assessment: heart rate, PR interval, RR interval, QT interval, corrected QT interval according to Fridericia's formula (QTcF), corrected QT interval according to Bazett's formula (QTcB), QRS duration, and QRS axis. The count of participants with potentially clinically significant ECG findings is reported.

  Day 1 (start of tbo-filgrastim administration) pre-dose, 4 hours post dose and 6 hours post dose; Day 21 (end of study visit)

• Participants With Negative Shifts From Baseline to End of Study in Physical Exam Findings

  Physical examination was performed at screening and at the end-of-study visit. The following body systems were marked as normal or abnormal and if abnormal, whether clinically significant: Head, ears, eyes, nose and throat (HEENT), chest and lungs, heart, abdomen, skin, lymph nodes and neurological. Any physical examination finding that is judged by the investigator as a clinically significant change (worsening) compared with a baseline value were considered as an adverse event. Counts of participants with a negative shift from baseline in any of the body systems (including shifts from normal to abnormal, not clinically significant) are presented.

  Baseline: Day -21, Day 21 (end of study visit)

• Participants With Injection Site Reactions to Tbo-Filgrastim Administration

  Using Local Tolerability Assessment Scale ranging from Pain severity 0 (Absent) to 3 (Spontaneously painful)

  Day 1 (start of tbo-filgrastim administration) up to Day 14

• Participants With Negative Shifts From Baseline to End of Study in Spleen Sonography Findings

  The investigator assessed spleen sonography findings as normal, abnormal not clinically significant, or abnormal clinically significant. Data representing counts of participants with a negative shift from baseline in spleen sonography findings (including shifts from normal to abnormal, not clinically significant) are presented.

  Baseline: Day -21, Day 21 (end of study visit)

• Participants Who Were Alive at the 90 Day Follow-Up

  Summary of participant survival at 90 day follow-up.

  90 days post end of study visit (111 days from start of tbo-filgrastim administration)

Secondary Outcomes (24)

• Participants With Positive Immunogenicity Findings Tested at Four Study Timepoints

  Baseline (Day -21), Day 21 (end of study visit), Day 51 (30 Day follow-up) and Day 111 (90 Day follow-up)

• Maximum Observed Serum Concentration (Cmax) of Tbo-Filgrastim

  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

• Time to Maximum Observed Serum Concentration (Tmax) of Tbo-Filgrastim

  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

• Area Under The Serum Concentration-Time Curve From Time 0 To Time Of Last Quantifiable Concentration (AUClast)

  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

• Area Under The Serum Concentration-Time Curve From Time 0 To 12 Hours Postdose (AUC0-12)

  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

Study Arms (1)

tbo-filgrastim

EXPERIMENTAL

Patients will receive subcutaneous doses of tbo-filgrastim 5 μg/kg body weight daily; each daily dose, to be administered at the investigative site

Drug: tbo-filgrastim

Interventions

tbo-filgrastim DRUG

5 μg/kg

tbo-filgrastim

Eligibility Criteria

• Age: 1 Month - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female infants, children and adolescents aged 1 month to \<16 years.
• Patients with solid tumors without bone marrow involvement, who are scheduled to receive myelosuppressive CTX.
• Body weight ≥5 kg.
• 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
• 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.
• Normal cardiac, renal, and hepatic function.
• All subjects must have a life expectancy of 12 weeks or more.
• Performance Status: Lansky performance score \>60 (age 1 to \<16 years).
• More criteria may apply, please contact the investigator for more information.

You may not qualify if:

• Bone marrow involvement.
• Active myelogenous leukemia or history of myelogenous leukemia.
• 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.
• History of congenital neutropenia or cyclic neutropenia.
• Pregnant or nursing female patients.
• 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.
• Ongoing active infection or history of infectious disease within 2 weeks prior to the screening visit.
• Treatment with lithium at screening or planned during the study
• More criteria may apply, please contact the investigator for more information.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (33)

Teva Investigational Site 12958

Long Beach, California, 90806, United States

Location

Teva Investigational Site 12951

Los Angeles, California, 90024, United States

Location

Teva Investigational Site 12954

Jackson, Mississippi, 39216, United States

Location

Teva Investigational Site 12953

Las Vegas, Nevada, 89109, United States

Location

Teva Investigational Site 12959

Valhalla, New York, 10595, United States

Location

Teva Investigational Site 12960

Columbus, Ohio, 43205, United States

Location

Teva Investigational Site 12957

Houston, Texas, 77030, United States

Location

Teva Investigational Site 59104

Sofia, 15257, Bulgaria

Location

Teva Investigational Site 59105

Varna, 9010, Bulgaria

Location

Teva Investigational Site 60015

Rijeka, 51000, Croatia

Location

Teva Investigational Site 60014

Zagreb, 10000, Croatia

Location

Teva Investigational Site 60016

Zagreb, 10000, Croatia

Location

Teva Investigational Site 51186

Budapest, 1089, Hungary

Location

Teva Investigational Site 51185

Budapest, 1094, Hungary

Location

Teva Investigational Site 51184

Szeged, 6725, Hungary

Location

Teva Investigational Site 53249

Gdansk, 80-952, Poland

Location

Teva Investigational Site 53248

Lublin, 20-093, Poland

Location

Teva Investigational Site 53245

Warsaw, 01-211, Poland

Location

Teva Investigational Site 53246

Warsaw, 04-730, Poland

Location

Teva Investigational Site 53247

Wroclaw, 50-556, Poland

Location

Teva Investigational Site 52063

Bucharest, 022328, Romania

Location

Teva Investigational Site 52064

Cluj-Napoca, Cluj, 400015, Romania

Location

Teva Investigational Site 52065

Timișoara, 300383, Romania

Location

Teva Investigational Site 50282

Chelyabinsk, 454076, Russia

Location

Teva Investigational Site 50281

Krasnodar, 350007, Russia

Location

Teva Investigational Site 50284

Moscow, 117198, Russia

Location

Teva Investigational Site 50280

Saint Petersburg, 197110, Russia

Location

Teva Investigational Site 50283

Volgograd, 400138, Russia

Location

Teva Investigational Site 58147

Kharkiv, 61070, Ukraine

Location

Teva Investigational Site 58145

Kyiv, 03022, Ukraine

Location

Teva Investigational Site 58148

Lviv, 79035, Ukraine

Location

Teva Investigational Site 58146

Vinnytsia, 21029, Ukraine

Location

Teva Investigational Site 58149

Vinnytsia, 21029, Ukraine

Location

MeSH Terms

Conditions

Neutropenia

Interventions

Filgrastim

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

USMedInfo@tevapharm.com

215-591-3000

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2014
• First Posted: July 15, 2014
• Study Start: May 12, 2015
• Primary Completion: April 4, 2017
• Study Completion: April 4, 2017
• Last Updated: December 10, 2021
• Results First Posted: July 31, 2018

Record last verified: 2021-12

Locations

US (7); HU (3); RO (3); RU (5); BU (2); PL (5); CR (3); UA (5)