PK/PD of XM22 in Children With Ewing Family of Tumors or Rhabdomyosarcoma

Multicenter, Open-label Study to Assess the Pharmacokinetics (PK), Pharmacodynamics (PD), Efficacy, Safety, Tolerability, and Immunogenicity of a Single, Subcutaneous Dose of 100µg/kg XM22 in 21 Children With Ewing Family of Tumors or Rhabdomyosarcoma

This is a Phase I, open label study aimed at assessing the pharmacokinetics, pharmacodynamics, the efficacy, safety, and tolerability of a single injection of XM22 in children with Ewing family of tumors or rhabdomyosarcoma scheduled to receive chemotherapy (CTX)

Study Overview

• Status: Completed
• Conditions: Ewing Family of Tumors, Rhabdomyosarcoma
• Intervention / Treatment: Drug: Lipegfilgrastim

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • Teva Investigational Site 0103
  • Sofia, Bulgaria
    • Teva Investigational Site 0101
  • Varna, Bulgaria
    • Teva Investigational Site 0102
• Czech Republic
  • Praha 5, Czech Republic
    • Teva Investigational Site 0201
• Hungary
  • Budapest, Hungary
    • Teva Investigational Site 0301
• Poland
  • Lublin, Poland
    • Teva Investigational Site 0401
• Russian Federation
  • Chelyabinsk, Russian Federation
    • Teva Investigational Site 0501
  • Ekaterinburg, Russian Federation
    • Teva Investigational Site 0504
  • Krasnodar, Russian Federation
    • Teva Investigational Site 0507
  • Moscow, Russian Federation
    • Teva Investigational Site 0505
  • Moscow, Russian Federation
    • Teva Investigational Site 0506
  • Moscow, Russian Federation
    • Teva Investigational Site 0508
  • St. Petersburg, Russian Federation
    • Teva Investigational Site 0502
• Ukraine
  • Dnipropetrovsk, Ukraine
    • Teva Investigational Site 0701
  • Donetsk, Ukraine
    • Teva Investigational Site 0705
  • Kharkiv, Ukraine
    • Teva Investigational Site 0702
  • Kyiv, Ukraine
    • Teva Investigational Site 0704
  • Lviv, Ukraine
    • Teva Investigational Site 0703

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female children and adolescents aged 2 to <18 years
• Written informed consent provided by parent(s)/legal representative(s) of the pediatric patient and patient's assent if appropriate
• Able to understand and/or follow study instructions alone or with parental assistance
• Diagnosed with the Ewing family of tumors or Rhabdomyosarcoma
• Scheduled to receive 1 of the following CTX regimens (inpatient or outpatient)

• For the Ewing family of tumors:

  • vincristine/ifosfamide/doxorubicin/etoposide (VIDE); with concomitant sodium 2-mercaptoethane sulfonate (MESNA) according to local standards
  • vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide (VDC/IE); with concomitant MESNA treatment according to local standards

• For rhabdomyosarcoma:

  • vincristine/actinomycin/cyclophosphamide (VAC)
  • vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide (VDC/IE); with concomitant MESNA treatment according to local standards
• Chemotherapy-naïve
• Body weight ≥15 kg
• White blood cell (WBC) count >2.5 x 109/L, absolute neutrophil count (ANC) ≥1.5 x 109/L, and platelet count ≥100 x 109/L (at screening and prior to CTX)
• For patients aged ≥12 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (See Appendix A.)
• Fertile patients (male or female) must use highly reliable contraceptive measures (i.e. two of the following: oral contraception, implants, injections, barrier contraception, and intrauterine device, or vasectomized/sterilized partners, or sexual abstinence). For purposes of this study, a fertile female patient is any female patient who has experienced menarche and who has not undergone tubal ligation.
• Female patients who have attained menarche must have a negative urine pregnancy test at the screening visit.

Exclusion Criteria:

• Previous exposure to filgrastim, pegfilgrastim or lenograstim or other G-CSFs in clinical development within 6 months prior to the XM22 administration
• Known hypersensitivity to filgrastim, pegfilgrastim or lenograstim or any other G-CSF in clinical development
• History of congenital neutropenia or cyclic neutropenia
• Any illness or condition that in the opinion of the Investigator may affect the safety of the patient or the evaluation of any study endpoint
• Pregnant or nursing women
• Fertile patients who do not agree to use highly reliable contraceptive measures during the entire duration of the study
• Prior bone marrow or stem cell transplant, or prior radiation to ≥25% of bone marrow (e.g. whole pelvic radiation) for any reason, or any therapeutic radiation within the 3 weeks prior to the XM22 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XM22, 100 μg/kg BW	Drug: Lipegfilgrastim; Lipegfilgrastim 100ug/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Area under the curve, Maximum observed serum concentration (Cmax), Rate constant associated with terminal phase, Mean Residence Time, Time to reach Cmax, and Apparent volume of distribution during terminal phase after non-intravenous administration	A total of 7 PK samples will be obtained at prespecified periods	16 months

Secondary Outcome Measures

Outcome Measure	Time Frame
PD:Absolute Neutrophil Count	16 months

Collaborators and Investigators

• Sponsor: Merckle GmbH
• Investigators: Study Director: Andreas Lammerich, MD, Merckle GmbH, Teva Ratiopharm

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: April 18, 2012
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (Estimate): April 26, 2012

Study Record Updates

• Last Update Posted (Estimate): May 18, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Neuroectodermal Tumors, Primitive; Neoplasms, Muscle Tissue; Myosarcoma; Sarcoma, Ewing; Rhabdomyosarcoma; Neuroectodermal Tumors, Primitive, Peripheral
• Other Study ID Numbers: XM22-07; 2011-004742-18 (EudraCT Number)