Methylprednisolone Sodium Succinate in Treating Patients With Acute Graft-versus-Host Disease of the Gastrointestinal Tract

Acute Graft Versus Host Disease Clinical Trial

Official title:

Intra-Arterial Steroid Administration of De Novo Acute Graft-vs-Host Disease of the Gastrointestinal Tract: A Phase II Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02425813
• Other study ID #: IRB00032434
• Secondary ID: NCI-2015-00548CC
• Status: Withdrawn
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: July 2016

Study information

• Verified date: July 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well methylprednisolone sodium succinate works in treating patients with graft-versus-host disease (GVHD) of the gastrointestinal tract that has begun within 100 days of transplant (acute GVHD). Corticosteroids are a type of drug that reduces inflammation. Giving corticosteroid drugs, such as methylprednisolone sodium succinate, directly into the arteries of the gastrointestinal tract may help treat inflammation caused by GVHD. Giving methylprednisolone sodium succinate in addition to standard treatments may be more effective in treating GVHD.

Description:

PRIMARY OBJECTIVES:

I. To assess the efficacy of intra-arterial steroid administration (IASA) with methylprednisolone sodium succinate (MePDSL) in this dose-schedule for treatment of de novo acute moderate-to-severe GvHD of the gastrointestinal tract (GIT).

SECONDARY OBJECTIVES:

I. To assess the safety of IASA MePDSL in this dose-schedule for treatment of de novo acute moderate-to-severe acute GvHD of the GIT.

II. To assess the feasibility of IASA MePDSL in this dose-schedule for treatment of de novo acute moderate-to-severe acute GvHD of the GIT.

OUTLINE:

STUDY AGENT: Patients receive methylprednisolone sodium succinate intra-arterially (IA) once daily (QD) on days 1-3.

CONVENTIONAL THERAPY: Patients also receive conventional therapy comprising methylprednisolone sodium succinate intravenously (IV) every 12 hours on for 7-14 days beginning on day 1 and budesonide PO on days 1-56. Patients with response by day 7-14 may begin taper and receive methylprednisolone orally (PO) on days 28-56. Treatment continues in the absence of disease progression or unacceptable toxicity.

IMMUNOSUPPRESSIVE THERAPY (IST): Patients receive conventional IST or continue their previous prophylactic regimen beginning on day 1 to 56 (or beyond) at the discretion of the treating physician.

After completion of study treatment, patients are followed up for 360 days.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of acute GvHD of the GIT (any site except isolated "upper" GIT disease); other sites may be involved as well; their presence will not influence eligibility

• Biopsies are strongly recommended and should be obtained, ideally, by full endoscopy including esophagogastroduodenoscopy (EGD) and flexible sigmoidoscopy or colonoscopy

• However, and with an appropriate clinical presentation, it is desirable -- but not necessary -- to have pathology confirmation

• If other diagnoses are excluded, it is not necessary to biopsy all potentially involved sites in the GIT to initiate therapy

• It is possible that other diagnoses may be present as well, and this should not exclude eligibility so long as they are distinct (this statement is generic, but applies especially to various types of infective colitis; that said, on-going anti-infective therapy must be on-going)

• Any diagnosis, donor or source of hematopoietic stem cells (HSC) is allowed, including donor leukocyte infusions (DLI)

• Prior or on-going therapy:

• De novo disease with no previous systemic (topical allowed) therapy for acute GvHD --except for a maximum (and ideally much less) of 72 hours of prior glucocorticoid (GC) therapy, > 0.5 mg/kg/day of MePDSL or equivalent after the onset of acute GvHD

• An exception to the above exists for patients with prior acute GvHD (of any site) who received GC therapy, experienced a complete response (CR), were tapered off GC and recurred >= 15 days later; such are eligible after review by the principal investigator (PI) or his designee

• The use of on-going acute GvHD prophylaxis will be continued

• The use of any other IST is allowed if acute GvHD of the GIT develops while the patient is off all IST; IST may be started at the discretion of the attending physician after discussion with the PI of this study

• Treatment with oral budesonide is to be started or continued at full dose

• Please consult with the study PI regarding any questions or concerns of study eligibility

• No specific organ function parameters are required; however, significant abnormalities should be discussed with the study PI

• Ability to understand and the willingness to sign the Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria:

• Significant risk factors for IASA therapy including, but not limited to: major uncorrectable coagulopathy, bowel perforation, ongoing bacteremia, mesenteric insufficiency, etc; in these or any questionable cases, discussion with the PI is recommended

• Patients may not be receiving any other drugs for the treatment of GvHD or investigational agents, except for a maximum of 72 hours of prior GC therapy, as above

• Uncontrolled, severe infective processes

• Patients with relapsed or persistent malignancy requiring immunosuppressive withdrawal or modulation (an example of this may be a patient who relapsed and was being treatment with DLI and then developed GvHD)

• Pregnant women are excluded from this study; breastfeeding should be discontinued

Related Conditions & MeSH terms

• Acute Graft Versus Host Disease
• Graft vs Host Disease
• Intestinal Graft Versus Host Disease

Intervention

Drug:
• Budesonide
Given PO
• Methylprednisolone Sodium Succinate
Given IA and IV

Locations

Country	Name	City	State
United States	Comprehensive Cancer Center of Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence		Day 56
Primary	Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence		By day 180
Primary	Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence		By day 360
Primary	Proportions of response among surviving patients		Day 14
Primary	Proportions of progression among surviving patients		Day 14
Primary	Rate of acute (and/or chronic) GvHD-free survival	Simon's two-stage design will be used. The null hypothesis that the true CR rate is 30% will be tested against a one-sided alternative and presented with a 95% confidence interval.	Day 56
Primary	Proportions of response among surviving patients		Day 28
Primary	Proportions of progression among surviving patients		Day 28
Secondary	Daily and cumulative GC dose	Descriptive measures will be provided at each time point specified.	Day 28
Secondary	Feasibility	Feasibility will be defined as less than three IASA sessions for any reason and obvious procedure-related problems in >= 10% of patients. Descriptive measures will be provided at each time point specified.	Up to day 360
Secondary	GvHD-free survival	Descriptive measures will be provided at each time point specified. Survival estimates will be calculated using Kaplan-Meier estimation.	Day 180
Secondary	GvHD-free survival	Descriptive measures will be provided at each time point specified. Survival estimates will be calculated using Kaplan-Meier estimation.	Day 360
Secondary	Incidence of acute GvHD "flare" after CR/PR requiring modification and/or additional agents (and/or 2.5 mg/kg/day of prednisone [or methylprednisolone equivalent of 2 mg/kg/day]) for systemic therapy	Descriptive measures will be provided at each time point specified.	Up to day 56
Secondary	Incidence of chronic GvHD	Descriptive measures will be provided at each time point specified.	By day 180
Secondary	Incidence of chronic GvHD	Descriptive measures will be provided at each time point specified.	By day 360
Secondary	Incidence of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 toxicities	Frequencies of toxicities grade 2 or higher will be totaled at the conclusion of the study.	Up to day 360
Secondary	Incidence of opportunistic infections	Descriptive measures will be provided at each time point specified.	Day 180
Secondary	Non-relapse mortality (NRM)	Descriptive measures will be provided at each time point specified.	Day 180
Secondary	NRM	Descriptive measures will be provided at each time point specified.	Day 360
Secondary	Overall survival	Descriptive measures will be provided at each time point specified. Survival estimates will be calculated using Kaplan-Meier estimation.	Day 180
Secondary	Overall survival	Descriptive measures will be provided at each time point specified. Survival estimates will be calculated using Kaplan-Meier estimation.	Day 360