Clinical trial NCT00258180: Cyclophosphamide in Treating Young Patients With Severe Autoimmune Enteropathy
Official title: High-Dose Cyclophosphamide for the Treatment of Severe Autoimmune Enteropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diarrhea
Gastrointestinal Complications
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: unspecified childhood solid tumor, protocol specific
gastrointestinal complications
diarrhea
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-11-24
Enrollment: 3
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Treatment-free Remission at 1 Year After Study Completion
timeFrame: 1 year
measure: Number of Participants Experiencing Intervention-related Adverse Events, as Defined by CTCAE at 1 Month
timeFrame: 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: David M. Loeb, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Maria Oliva-Hemker, MD
role: PRINCIPAL_INVESTIGATOR
References: