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

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Ewing Family of Tumors, Rhabdomyosarcoma

Intervention / Treatment
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* Drug: Lipegfilgrastim


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XM22, 100 μg/kg BW<br> | Drug: Lipegfilgrastim<br>* Lipegfilgrastim 100ug/kg<br>|

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| PD:Absolute Neutrophil Count |  | 16 months |