Clinical trial NCT01585649: PK/PD of XM22 in Children With Ewing Family of Tumors or Rhabdomyosarcoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ewing Family of Tumors, Rhabdomyosarcoma
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-26
Enrollment: 21
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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)


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 16 months
Secondary outcomes:
measure: PD:Absolute Neutrophil Count
timeFrame: 16 months
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Teva Investigational Site 0103
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 0101
city: Varna
country: Bulgaria
facility: Teva Investigational Site 0102
city: Praha 5
country: Czech Republic
facility: Teva Investigational Site 0201
city: Budapest
country: Hungary
facility: Teva Investigational Site 0301
city: Lublin
country: Poland
facility: Teva Investigational Site 0401
city: Chelyabinsk
country: Russian Federation
facility: Teva Investigational Site 0501
city: Ekaterinburg
country: Russian Federation
facility: Teva Investigational Site 0504
city: Krasnodar
country: Russian Federation
facility: Teva Investigational Site 0507
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 0505
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 0506
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 0508
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 0502
city: Dnipropetrovsk
country: Ukraine
facility: Teva Investigational Site 0701
city: Donetsk
country: Ukraine
facility: Teva Investigational Site 0705
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 0702
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 0704
city: Lviv
country: Ukraine
facility: Teva Investigational Site 0703
Study officials:
affiliation: Merckle GmbH, Teva Ratiopharm
name: Andreas Lammerich, MD
role: STUDY_DIRECTOR
References: