Cyclophosphamide in Treating Young Patients With Severe Autoimmune Enteropathy

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00258180
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 3
• Location: 1
• Arm: 1
• Actual Duration (Months): 42.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diarrhea; Gastrointestinal Complications; Unspecified Childhood Solid Tumor, Protocol Specific	Biological: filgrastim; Drug: cyclophosphamide	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: High-Dose Cyclophosphamide for the Treatment of Severe Autoimmune Enteropathy
• Actual Study Start Date: Aug 15, 2005
• Actual Primary Completion Date: Feb 24, 2009
• Actual Study Completion Date: Feb 24, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-free Remission at 1 Year After Study Completion [1 year]

   Number of participants off therapy 1 year after study completion without relapse.

2. Number of Participants Experiencing Intervention-related Adverse Events, as Defined by CTCAE at 1 Month [1 month]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410

Sponsors and Collaborators

• Johns Hopkins University
• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00258180
• Other Study ID Numbers: 03-07-08-04; P30CA006973; JHOC-J0326; J0326; CDR0000441133
• First Posted: Nov 24, 2005
• Last Update Posted: Apr 16, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Johns Hopkins University: unspecified childhood solid tumor, protocol specific; gastrointestinal complications; diarrhea
• Additional relevant MeSH terms: Diarrhea; Cyclophosphamide

Study Results

Participant Flow

Pre-assignment Detail	1 subject was not assigned intervention due to PI decision.

Arm/Group Title	Severe Autoimmune Enteropathy
Arm/Group Description	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.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Severe Autoimmune Enteropathy
Arm/Group Description	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.
Overall Participants	2
Age (Count of Participants)
<=18 years	2 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-free Remission at 1 Year After Study Completion
Description	Number of participants off therapy 1 year after study completion without relapse.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Severe Autoimmune Enteropathy
Arm/Group Description	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.
Measure Participants	2
Count of Participants [Participants]	2 100%

2. Primary Outcome

Title	Number of Participants Experiencing Intervention-related Adverse Events, as Defined by CTCAE at 1 Month
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Severe Autoimmune Enteropathy
Arm/Group Description	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 filgrastim: Administered IV or subcutaneously once daily beginning on day 10 and continuing for 3 days or until blood counts recover cyclophosphamide: Administered IV over 1 hour on days 1-4
Measure Participants	2
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	up to 1 year post-intervention
Arm/Group Title	Severe Autoimmune Enteropathy
Arm/Group Description	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
All Cause Mortality
	Severe Autoimmune Enteropathy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Severe Autoimmune Enteropathy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Severe Autoimmune Enteropathy
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.