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

January 24, 2017 updated by: Paul Martin, Fred Hutchinson Cancer Center

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient with a diagnosis of severe intestinal GVHD that is not improving at any time after initial treatment with glucocorticoids for at least 7 days are eligible for enrollment; measures indicating severity of GVHD will include: a) persistent diarrhea with average daily stool volumes > 500 mL per day; or b) persistent hemorrhage that is detectable by visual inspection of the stool
  • Patients with denuded mucosa caused by GVHD are eligible for enrollment, regardless of prior treatment for acute GVHD; denuded mucosa is defined as loss (i.e., erosion or sloughing) of the epithelium in: a) at least one-third of the surface area in a 30 cm colonic segment (i.e., rectosigmoid, descending or transverse colon); or b) at least one fifth of the surface area of the second portion of the duodenum, as estimated by endoscopic evaluation; denuded mucosa must be documented by images of the duodenum and colon and by histologic evaluation of the colon
  • All subjects must provide written informed consent with the use of forms approved by the Fred Hutchinson Cancer Research Center (FHCRC) Institutional Review Board (IRB)

Exclusion Criteria:

  • Significant renal dysfunction (estimated creatinine clearance < 30 mL/min)
  • Persistent or recurrent malignancy
  • Secondary malignancy
  • Patients who had autologous or syngeneic marrow transplantation
  • Presence of any cause of intestinal symptoms or ulceration other than GVHD
  • Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol will be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: lithium carbonate
Given orally
Other Names:
  • Lithobid
  • Eskalith
  • Lithium
  • Lithane
  • Lithonate
  • Lithotabs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
at 28 days after starting treatment with the study product

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 6 months
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.
2 to 3 weeks after starting treatment with the study product
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.
4 weeks after starting treatment with the study product
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.
5 weeks after starting treatment with the study product
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.
6 to 7 weeks after starting treatment with the study product
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. Failure to respond was defined as failure to meet partial response criteria.
9 to 11 weeks after starting treatment with the study product
Recurrent or Progressive Malignancy
Time Frame: 2 years after enrollment
Recurrence or progression of the malignant disease that was the reason for hematopoietic cell transplantation
2 years after enrollment
Non-relapse Mortality
Time Frame: 2 years after enrollment
Death without prior recurrent or progressive malignancy after transplantation.
2 years after enrollment
Survival
Time Frame: 6 months after enrollment
Patients who were alive at the specified time after enrollment
6 months after enrollment
Survival
Time Frame: 1 year after enrollment
Patients who were alive at the specified time point
1 year after enrollment
Survival
Time Frame: 2 years after enrollment
Patients who were alive at the specified time point
2 years after enrollment
Causes of Death
Time Frame: up to 6 years after enrollment
Medical condition that made the greatest contribution in causing death
up to 6 years after enrollment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Agents Added to Treat GVHD More Than 3 Days After Enrollment
Time Frame: Up to 100 days after enrollment
Any systemic medication given in an effort to control graft-versus-host disease
Up to 100 days after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Paul Martin, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

December 6, 2006

First Submitted That Met QC Criteria

December 6, 2006

First Posted (Estimate)

December 7, 2006

Study Record Updates

Last Update Posted (Actual)

March 7, 2017

Last Update Submitted That Met QC Criteria

January 24, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2080.00
  • NCI-2010-00269

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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