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

NCT02425813 | Withdrawn Phase 2 FDA Drug

• 4 other identifiers: IRB00032434NCI-2015-00548CCCWFU 98115P30CA012197
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Graft Versus Host Disease; Intestinal Graft Versus Host Disease

Outcome Measures

Primary Outcomes (8)

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

  Day 56

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

  By day 180

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

  By day 360

• Proportions of response among surviving patients

  Day 14

• Proportions of progression among surviving patients

  Day 14

• 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

• Proportions of response among surviving patients

  Day 28

• Proportions of progression among surviving patients

  Day 28

Secondary Outcomes (13)

• Daily and cumulative GC dose

  Day 28

• Feasibility

  Up to day 360

• GvHD-free survival

  Day 180

• GvHD-free survival

  Day 360

• 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

  Up to day 56

Study Arms (1)

Treatment (methylprednisolone sodium succinate, budesonide)

EXPERIMENTAL

STUDY AGENT: Patients receive methylprednisolone sodium succinate IA QD on days 1-3. CONVENTIONAL THERAPY: Patients also receive conventional therapy comprising methylprednisolone sodium succinate 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 PO on days 28-56. Treatment continues in the absence of disease progression or unacceptable toxicity. 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.

Drug: Budesonide; Drug: Methylprednisolone Sodium Succinate

Interventions

Budesonide DRUG

Given PO

Also known as: Budecort, Butacort, Eltair, Nasocort, Preferid, Pulmicort, Pulmicort Turbuhaler, Rhinocort

Treatment (methylprednisolone sodium succinate, budesonide)

Methylprednisolone Sodium Succinate DRUG

Given IA and IV

Also known as: A-MethaPred, Asmacortone, Cryosolona, Medrate, Metypred, Prednilem, Solu Moderin, Solu-Medrol, Solu-Medrone

Treatment (methylprednisolone sodium succinate, budesonide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Interventions

Budesonide; Methylprednisolone Hemisuccinate; Methylprednisolone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols; Pregnadienes

Study Officials

• Gordon Phillips

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 24, 2015
• Study Start: October 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 2, 2018

Record last verified: 2018-07

Locations

US (1)