Cyclophosphamide in Treating Young Patients With Severe Autoimmune Enteropathy

High-Dose Cyclophosphamide for the Treatment of Severe Autoimmune Enteropathy

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific; Diarrhea; Gastrointestinal Complications
• Intervention / Treatment: Biological: filgrastim; Drug: cyclophosphamide

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: severe autoimmune enteropathy; 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; Administered IV or subcutaneously once daily beginning on day 10 and continuing for 3 days or until blood counts recover; Other Names: G-CSF; Drug: cyclophosphamide; Administered IV over 1 hour on days 1-4

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David M. Loeb, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Principal Investigator: Maria Oliva-Hemker, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2005
• Primary Completion (Actual): February 24, 2009
• Study Completion (Actual): February 24, 2009

Study Registration Dates

• First Submitted: November 22, 2005
• First Submitted That Met QC Criteria: November 22, 2005
• First Posted (Estimate): November 24, 2005

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: March 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific; diarrhea; gastrointestinal complications
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: 03-07-08-04; P30CA006973 (U.S. NIH Grant/Contract); JHOC-J0326 (Other Identifier: SKCCC); J0326 (Other Identifier: SKCCC); CDR0000441133 (Registry Identifier: NCI PDQ)