Clinical trial NCT02425813: Methylprednisolone Sodium Succinate in Treating Patients With Acute Graft-versus-Host Disease of the Gastrointestinal Tract
Official title: Intra-Arterial Steroid Administration of De Novo Acute Graft-vs-Host Disease of the Gastrointestinal Tract: A Phase II Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Acute Graft Versus Host Disease
Intestinal Graft Versus Host Disease
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-04-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence
timeFrame: Day 56
measure: Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence
timeFrame: By day 180
measure: Incidence of discontinuation of systemic GCs without acute GvHD flare and without disease progression/recurrence
timeFrame: By day 360
measure: Proportions of response among surviving patients
timeFrame: Day 14
measure: Proportions of progression among surviving patients
timeFrame: Day 14
measure: Rate of acute (and/or chronic) GvHD-free survival
timeFrame: Day 56
measure: Proportions of response among surviving patients
timeFrame: Day 28
measure: Proportions of progression among surviving patients
timeFrame: Day 28
Secondary outcomes:
measure: Daily and cumulative GC dose
timeFrame: Day 28
measure: Feasibility
timeFrame: Up to day 360
measure: GvHD-free survival
timeFrame: Day 180
measure: GvHD-free survival
timeFrame: Day 360
measure: 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
timeFrame: Up to day 56
measure: Incidence of chronic GvHD
timeFrame: By day 180
measure: Incidence of chronic GvHD
timeFrame: By day 360
measure: Incidence of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 toxicities
timeFrame: Up to day 360
measure: Incidence of opportunistic infections
timeFrame: Day 180
measure: Non-relapse mortality (NRM)
timeFrame: Day 180
measure: NRM
timeFrame: Day 360
measure: Overall survival
timeFrame: Day 180
measure: Overall survival
timeFrame: Day 360
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Gordon Phillips
role: PRINCIPAL_INVESTIGATOR
References: