Clinical Trial: Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease (GVHD) After Donor Stem Cell Transplant

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study to Evaluate the Potential Efficacy of Lithium Carbonate for Stimulation of Intestinal Recovery In Patients With Acute Graft-versus-host Disease (GVHD)

Brief Summary:

RATIONALE: Lithium carbonate may be an effective treatment for intestinal graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This clinical trial is studying lithium carbonate in treating patients with acute intestinal graft-versus-host-disease after donor stem cell transplant.


Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the effects of lithium on functional and mucosal anatomic recovery in the small or large bowel of patients with acute GVHD.

II. Functional recovery will be evaluated according to changes in clinical manifestations of gastrointestinal GVHD. III. Mucosal anatomic recovery will be evaluated by review of results from clinically indicated endoscopic evaluations.

SECONDARY OBJECTIVES:

I. To assess the tolerability of lithium administration in allogeneic hematopoietic cell transplant recipients.

OUTLINE: Patients receive oral lithium carbonate once or twice daily. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.


Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Functional Recovery [ Time Frame: at 28 days after starting treatment with the study product ]

Functional recovery was defined as partial or complete resolution of gastrointestinal manifestations of acute graft-versus-host disease. Gastrointestinal manifestations of acute graft-versus-host disease include anorexia, nausea, vomiting, diarrhea, abdominal pain and bleeding. Complete response (CR) of intestinal GVHD was defined as the absence of any symptoms referable to intestinal GVHD. Partial response (PR) was defined as clearing of abdominal pain (or withdrawal of opioid analgesic requirements in patients treated for abdominal pain) and of grossly visible bleeding if present, and resolution of diarrhea or decrease in the three day average stool volume by ≥ 500 mL in patients with stool volumes of ≥ 500 mL. Progression of GVHD was defined as an increase in the three day average stool volume by > 500 mL, or the development of new abdominal pain (or new opioid analgesic requirements) or new intestinal bleeding.


Original Primary Outcome:

  • Functional recovery as measured by clinical response
  • Mucosal anatomic recovery as assessed by esophagogastroduodenoscopy (EGD), colonoscopy, sigmoidoscopy, or biopsy specimens of the colon


Current Secondary Outcome:

  • Duration of Treatment With the Study Product [ Time Frame: Up to 6 months ]
    Number of days from beginning of orally administered lithium carbonate to the end of orally administered lithium carbonate
  • Mucosal Anatomic Recovery [ Time Frame: 2 to 3 weeks after starting treatment with the study product ]
    Endoscopic evaluation of improvement. Categories include 1) no improvement, 2) regenerative changes, 3) limited improvement, 4) partial improvement and 5) complete response. Endoscopic manifestations of acute graft-versus-host disease include edema, erythema, mucosal ulceration and denudation. Complete mucosal recovery was defined as the appearance of intact mucosa with at least 98% of the luminal surface covered by epithelium. Partial response was defined as the appearance of mostly intact mucosa with at least 80% improvement or less than 10% denuded. Limited response was retrospectively designated to describe visible improvement that was less than partial response. Regenerative change was retrospectively designated to describe early reappearance of mucosal integrity in a previously denuded area but not sufficient to meet criteria for partial response. Failure to respond was defined as failure to meet partial response criteria.
  • Mucosal Anatomic Recovery [ Time Frame: 4 weeks after starting treatment with the study product ]
    Endoscopic evaluation of improvement. Categories include 1) no improvement, 2) regenerative changes, 3) limited improvement, 4) partial improvement and 5) complete response. Endoscopic manifestations of acute graft-versus-host disease include edema, erythema, mucosal ulceration and denudation. Complete mucosal recovery was defined as the appearance of intact mucosa with at least 98% of the luminal surface covered by epithelium. Partial response was defined as the appearance of mostly intact mucosa with at least 80% improvement or less than 10% denuded. Limited response was retrospectively designated to describe visible improvement that was less than partial response. Regenerative change was retrospectively designated to describe early reappearance of mucosal integrity in a previously denuded area but not sufficient to meet criteria for partial response. Failure to respond was defined as failure to meet partial response criteria.
  • Mucosal Anatomic Recovery [ Time Frame: 5 weeks after starting treatment with the study product ]
    Endoscopic evaluation of improvement. Categories include 1) no improvement, 2) regenerative changes, 3) limited improvement, 4) partial improvement and 5) complete response. Endoscopic manifestations of acute graft-versus-host disease include edema, erythema, mucosal ulceration and denudation. Complete mucosal recovery was defined as the appearance of intact mucosa with at least 98% of the luminal surface covered by epithelium. Partial response was defined as the appearance of mostly intact mucosa with at least 80% improvement or less than 10% denuded. Limited response was retrospectively designated to describe visible improvement that was less than partial response. Regenerative change was retrospectively designated to describe early reappearance of mucosal integrity in a previously denuded area but not sufficient to meet criteria for partial response. Failure to respond was defined as failure to meet partial response criteria.
  • Mucosal Anatomic Recovery [ Time Frame: 6 to 7 weeks after starting treatment with the study product ]
    Endoscopic evaluation of improvement. Categories include 1) no improvement, 2) regenerative changes, 3) limited improvement, 4) partial improvement and 5) complete response. Endoscopic manifestations of acute graft-versus-host disease include edema, erythema, mucosal ulceration and denudation. Complete mucosal recovery was defined as the appearance of intact mucosa with at least 98% of the luminal surface covered by epithelium. Partial response was defined as the appearance of mostly intact mucosa with at least 80% improvement or less than 10% denuded. Limited response was retrospectively designated to describe visible improvement that was less than partial response. Regenerative change was retrospectively designated to describe early reappearance of mucosal integrity in a previously denuded area but not sufficient to meet criteria for partial response. Failure to respond was defined as failure to meet partial response criteria.
  • Mucosal Anatomic Recovery [ Time Frame: 9 to 11 weeks after starting treatment with the study product ]
    Endoscopic evaluation of improvement. Categories include 1) no improvement, 2) regenerative changes, 3) limited improvement, 4) partial improvement and 5) complete response. Endoscopic manifestations of acute graft-versus-host disease include edema, erythema, mucosal ulceration and denudation. Complete mucosal recovery was defined as the appearance of intact mucosa with at least 98% of the luminal surface covered by epithelium. Partial response was defined as the appearance of mostly intact mucosa with at least 80% improvement or less than 10% denuded. Limited response was retrospectively designated to describe visible improvement that was less than partial response. Regenerative change was retrospectively designated to describe early reappearance of mucosal integrity in a previously denuded area but not sufficient to meet criteria for partial response.

    Original Secondary Outcome: Tolerability as assessed by NCI CTC version 2.0

    Information By: Fred Hutchinson Cancer Research Center

    Dates:
    Date Received: December 6, 2006
    Date Started: June 2006
    Date Completion:
    Last Updated: January 24, 2017
    Last Verified: January 2017