Beclomethasone Plus Prednisone in Treating Patients With Graft-Versus-Host Disease

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00043147

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

33.1

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Beclomethasone combined with prednisone may be an effective treatment for graft-versus-host disease caused by stem cell transplantation. It is not yet known if prednisone is more effective with or without beclomethasone in treating gastrointestinal graft-versus-host disease.

PURPOSE: Randomized phase III trial to determine the effectiveness of prednisone with or without beclomethasone in treating patients who have graft-versus-host disease afftecting the gastrointestinal system.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Drug: beclomethasone dipropionate Drug: methylprednisolone Drug: prednisone	Phase 3

Detailed Description

OBJECTIVES:

Compare the efficacy of beclomethasone dipropionate and prednisone vs placebo and prednisone, in terms of time to treatment failure, in patients with grade II graft-vs-host disease with gastrointestinal symptoms.
Compare the proportion of treatment failures on study days 10, 30, 50, 60, and 80 in patients treated with these regimens.
Compare the cumulative systemic corticosteroid exposure in patients treated with these regimens.
Compare the incidence and degree of hypothalamic-pituitary-adrenal axis suppression in patients treated with these regimens who have not experienced treatment failure by study day 50.
Compare the safety of these regimens in these patients.
Compare the total deaths and causes of death through 200 days post-transplantation of patients treated with these regimens.
Assess the pharmacokinetic profile of beclomethasone dipropionate in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, parallel, multicenter study. Patients are stratified according to graft tissue source (2 HLA haplotype-identical sibling vs all others) and topical steroid use at baseline (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral beclomethasone dipropionate 4 times daily on days 1-50. Patients also receive oral prednisone (or methylprednisolone IV) twice daily on days 1-10 with a rapid taper on days 11-17 followed by low-dose prednisone on days 18-80.
Arm II: Patients receive oral placebo 4 times daily on days 1-50. Patients also receive prednisone (or methylprednisolone) as in arm I.

In both arms, treatment continues in the absence of poorly controlled GVHD at day 10 or unacceptable toxicity.

Patients are followed at days 51, 60, and 80 and then at 200 days post-transplantation.

PROJECTED ACCRUAL: A total of 130 patients (65 per treatment arm) will be accrued for this study.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Supportive Care

Official Title:

A Phase III, Randomized, Placebo-Controlled, Multicenter Study of the Safety, Efficacy, and Pharmacokinetics of Oral Beclomethasone 17, 21-Dipropionate (BDP) in Conjunction With Ten Days of High-Dose Prednisone Therapy in the Treatment of Patients With Grade II Graft vs. Host Disease With Gastrointestinal Symptoms

Study Start Date :

Apr 1, 2002

Actual Study Completion Date :

Jan 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed graft-vs-host disease (GVHD) with gastrointestinal symptoms
Endoscopic evidence of grade II intestinal GVHD without another plausible etiology
Confirmed by biopsy of colon, stomach, small intestine, esophagus, or skin within 72 hours prior to study entry
At least 10 days post allogeneic hematopoietic stem cell transplantation
Received prior anti-candidal prophylaxis of the oropharynx with an effective drug
Confirmed absence of intestinal infection within the past 7 days
No liver GVHD with bilirubin greater than 3 mg/dL
No skin GVHD other than a slowly evolving rash that involves no more than 50% of the body surface
No more than 1,000 mL/day of diarrhea on any 1 day within the past 3 days

PATIENT CHARACTERISTICS:

Age

Not specified

Performance status

Not specified

Life expectancy

At least 3 months

Hematopoietic

Not specified

Hepatic

See Disease Characteristics

Renal

Not specified

Other

HIV negative
Able to swallow tablets
No multi-organ failure
No sepsis syndrome
No other condition with high mortality
No infection of the mouth or esophagus with a fungal organism
No persistent vomiting of oral intake
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
At least 30 days since prior biologic agents

Chemotherapy

Not specified

Endocrine therapy

At least 30 days since prior systemic (oral or parenteral) prescription corticosteroids administered for prophylaxis or treatment of GVHD or another inflammatory disease process
Concurrent dexamethasone as an antiemetic or to lessen side effects during medication or blood product administration allowed

Radiotherapy

Not specified

Surgery

See Disease Characteristics

Other

No prior beclomethasone dipropionate
At least 30 days since prior investigational drugs or devices
Concurrent immunosuppressants (e.g., cyclosporine, tacrolimus, sirolimus, methotrexate, or mycophenolate mofetil) allowed for GVHD prophylaxis