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

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.

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