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

Phase 1

Completed

• Conditions: Ewing Family of Tumors, Rhabdomyosarcoma
• Interventions: Drug: Lipegfilgrastim

• Registration Number: NCT01585649
• Lead Sponsor: Merckle GmbH

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-04-18
• Study First Submitted QC: 2012-04-23
• Study First Posted: 2012-04-26
• Study Start: 2012-07
• Primary Completion: 2014-06
• Study Completion: 2015-04
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-17
• Last Update Posted: 2016-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XM22, 100 μg/kg BW	Lipegfilgrastim	-

Primary Outcome Measures

Name	Time	Method
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	16 months	A total of 7 PK samples will be obtained at prespecified periods

Secondary Outcome Measures

Name	Time	Method
PD:Absolute Neutrophil Count	16 months

Trial Locations

Locations (18)

Teva Investigational Site 0103; 🇧🇬 Plovdiv, Bulgaria

Teva Investigational Site 0102; 🇧🇬 Varna, Bulgaria

Teva Investigational Site 0704; 🇺🇦 Kyiv, Ukraine

Teva Investigational Site 0101; 🇧🇬 Sofia, Bulgaria

Teva Investigational Site 0702; 🇺🇦 Kharkiv, Ukraine

Teva Investigational Site 0703; 🇺🇦 Lviv, Ukraine

Teva Investigational Site 0504; 🇷🇺 Ekaterinburg, Russian Federation

Teva Investigational Site 0701; 🇺🇦 Dnipropetrovsk, Ukraine

Teva Investigational Site 0507; 🇷🇺 Krasnodar, Russian Federation

Teva Investigational Site 0705; 🇺🇦 Donetsk, Ukraine

Teva Investigational Site 0401; 🇵🇱 Lublin, Poland

Teva Investigational Site 0501; 🇷🇺 Chelyabinsk, Russian Federation

Teva Investigational Site 0502; 🇷🇺 St. Petersburg, Russian Federation

Teva Investigational Site 0301; 🇭🇺 Budapest, Hungary

Teva Investigational Site 0201; 🇨🇿 Praha 5, Czech Republic

Teva Investigational Site 0505; 🇷🇺 Moscow, Russian Federation

Teva Investigational Site 0506; 🇷🇺 Moscow, Russian Federation

Teva Investigational Site 0508; 🇷🇺 Moscow, Russian Federation