Cyclophosphamide in Treating Young Patients With Severe Autoimmune Enteropathy

Study Overview
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Brief Summary
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RATIONALE: Cyclophosphamide may help control the symptoms of autoimmune enteropathy . PURPOSE: This phase II trial is studying how well cyclophosphamide works in treating young patients with severe autoimmune enteropathy.

Detailed Description
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OBJECTIVES: Primary Determine the rate of treatment-free remission in young patients with severe autoimmune enteropathy treated with high-dose cyclophosphamide. Secondary Determine the toxic effects of this drug in these patients. OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days 1-4. Patients then receive filgrastim (G-CSF) IV or subcutaneously once daily beginning on day 10 and continuing for 3 days or until blood counts recover. After completion of study treatment, patients are followed periodically for up to 1½ years. PROJECTED ACCRUAL: A total of 7-11 patients will be accrued for this study.

Official Title
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High-Dose Cyclophosphamide for the Treatment of Severe Autoimmune Enteropathy

Conditions
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Diarrhea, Gastrointestinal Complications, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: filgrastim
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of severe autoimmune enteropathy Condition is resistant to conventional therapy Histologic evidence of severe villous atrophy with intense lymphocytic infiltrate of the lamina propria by small intestinal biopsy within the past 3 months Disease failed to respond after ≥ 2 months of corticosteroid therapy at a dose of ≥ 0.5 mg/kg/day or ≥ 40 mg/day for patients > 20 kg AND 1 of the following therapies: Cyclosporine resulting in ≥ 1 whole blood level of > 200 ng/mL Tacrolimus resulting in ≥ 1 whole blood level of 5 ng/mL At least 50% estimated caloric needs provided by parenteral nutrition History of intractable diarrhea, defined as frequent watery stools for > 3 months that does not respond to dietary restriction No celiac disease, defined by a history of positive antiendomysial antibody or tissue transglutaminase antibody No primary immunodeficiency or x-linked autoimmunity-allergy dysregulation PATIENT CHARACTERISTICS: Performance status Lansky 60-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular Ejection fraction ≥ 40% OR shortening fraction ≥ 20% Pulmonary FVC or FEV_1 ≥ 50% of predicted (for patients > 8 years of age) No clinically abnormal pulmonary function or abnormal pulse oximetry (for patients ≤ 8 years of age) Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for at least 9 months after completion of study treatment No known chromosomal abnormality PRIOR CONCURRENT THERAPY: Biologic therapy No immunizations for at least 6 months after completion of study treatment Endocrine therapy See Disease Characteristics At least 5 days since prior corticosteroids No concurrent dexamethasone as an anti-emetic Other At least 5 days since other prior immunosuppressive medications (e.g., tacrolimus or cyclosporine)

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 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: severe autoimmune enteropathy<br>Young patients with severe autoimmune enteropathy receive cyclophosphamide IV over 1 hour on days 1-4. Patients then receive filgrastim (G-CSF) IV or subcutaneously once daily beginning on day 10 and continuing for 3 days or until blood counts recover | Biological: filgrastim<br>* Administered IV or subcutaneously once daily beginning on day 10 and continuing for 3 days or until blood counts recover<br>* Other names: G-CSF;Drug: cyclophosphamide<br>* Administered IV over 1 hour on days 1-4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-free Remission at 1 Year After Study Completion | Number of participants off therapy 1 year after study completion without relapse. | 1 year | 
| Number of Participants Experiencing Intervention-related Adverse Events, as Defined by CTCAE at 1 Month |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrointestinal complications, unspecified childhood solid tumor, protocol specific, diarrhea