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

Condition(s) targeted: Acute Graft Versus Host Disease; Intestinal Graft Versus Host Disease

Intervention: Budesonide (Drug); Methylprednisolone Sodium Succinate (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Comprehensive Cancer Center of Wake Forest University

Official(s) and/or principal investigator(s):
Gordon Phillips, Principal Investigator, Affiliation: Comprehensive Cancer Center of Wake Forest University

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.

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

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence

Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence

Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence

Proportions of response among surviving patients

Proportions of progression among surviving patients

Rate of acute (and/or chronic) GvHD-free survival

Proportions of response among surviving patients

Proportions of progression among surviving patients

Secondary outcome:

Daily and cumulative GC dose

Feasibility

GvHD-free survival

GvHD-free survival

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

Incidence of chronic GvHD

Incidence of chronic GvHD

Incidence of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 toxicities

Incidence of opportunistic infections

Non-relapse mortality (NRM)

NRM

Overall survival

Overall survival

Detailed 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina 27157, United States; Not yet recruiting
Gordon L. Phillips, Phone: 336-716-0659, Email: gophilli@wakehealth.edu
Gordon L. Phillips, Principal Investigator

Starting date: April 2015
Last updated: April 21, 2015