Accelerated Phase Chronic Myelogenous LeukemiaGVHDNCT00408681
Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease (GVHD) After Donor Stem Cell Transplant
A study testing lithium carbonate and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission
- What is being tested?
- lithium carbonate and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to 1 May 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
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)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- Being tested
- lithium carbonate, laboratory biomarker analysis
- Medical subject headings
- Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Blast Crisis, Pdgfra-Associated Chronic Eosinophilic Leukemia, Leukemia, Myelomonocytic, Chronic, Leukemia, Neutrophilic, Chronic, Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lithium carbonateDrug
Also called Eskalith, Lithane, Lithium, Lithobid
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Drug: lithium carbonate; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Recovery
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.
Measured: at 28 days after starting treatment with the study product
Secondary outcomes (12)
Duration of Treatment With the Study Product
Number of days from beginning of orally administered lithium carbonate to the end of orally administered lithium carbonate
Measured: Up to 6 months
Mucosal Anatomic Recovery
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.
Measured: 2 to 3 weeks after starting treatment with the study product
Mucosal Anatomic Recovery
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.
Measured: 4 weeks after starting treatment with the study product
Mucosal Anatomic Recovery
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.
Measured: 5 weeks after starting treatment with the study product
Mucosal Anatomic Recovery
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.
Measured: 6 to 7 weeks after starting treatment with the study product
Mucosal Anatomic Recovery
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.
Measured: 9 to 11 weeks after starting treatment with the study product
Recurrent or Progressive Malignancy
Recurrence or progression of the malignant disease that was the reason for hematopoietic cell transplantation
Measured: 2 years after enrollment
Non-relapse Mortality
Death without prior recurrent or progressive malignancy after transplantation.
Measured: 2 years after enrollment
Survival
Patients who were alive at the specified time after enrollment
Measured: 6 months after enrollment
Survival
Patients who were alive at the specified time point
Measured: 1 year after enrollment
Survival
Patients who were alive at the specified time point
Measured: 2 years after enrollment
Causes of Death
Medical condition that made the greatest contribution in causing death
Measured: up to 6 years after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2006 (estimated)
- Study startJun 2006
- Primary completionNov 2010
- Study completion1 May 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Accelerated Phase Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Paul Martin, Fred Hutchinson Cancer Center
- Investigators
- Paul Martin, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00408681
- Sponsor's protocol ID
- 2080.00
- Other IDs
- NCI-2010-00269
- Acronym
- GVHD
- Status last verified
- Jan 2017
- First submitted
- 6 Dec 2006
- Last updated
- 7 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Steinbach G, Hockenbery DM, Huls G, Furlong T, Myerson D, Loeb KR, Fann JR, Castilla-Llorente C, McDonald GB, Martin PJ. Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease. PLoS One. 2017 Aug 17;12(8):e0183284. doi: 10.1371/journal.pone.0183284. eCollection 2017.
PubMed 28817727
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00408681
- Acronym / sponsor ID
- GVHD / 2080.00
- Conditions
- Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2006
- Primary completion
- Nov 2010 (actual)
- Study completion
- 1 May 2015 (actual)
- First posted
- 7 Dec 2006 (estimated)
- Results
- Posted 20 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
PRIMARY OBJECTIVES:
- 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:
- 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 design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: lithium carbonate, Other: laboratory biomarker analysisPatients receive oral lithium carbonate once or twice daily. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lithium carbonateAlso: Eskalith, Lithane, Lithium, LithobidGiven orally | Drug | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
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.
12 secondary outcomes
Duration of Treatment With the Study Product
Time frame: Up to 6 months
Mucosal Anatomic Recovery
Time frame: 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
Mucosal Anatomic Recovery
Time frame: 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
Mucosal Anatomic Recovery
Time frame: 9 to 11 weeks after starting treatment with the study product
Recurrent or Progressive Malignancy
Time frame: 2 years after enrollment
Non-relapse Mortality
Time frame: 2 years after enrollment
Survival
Time frame: 6 months after enrollment
Survival
Time frame: 1 year after enrollment
Survival
Time frame: 2 years after enrollment
Causes of Death
Time frame: up to 6 years after enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28817727Steinbach G, Hockenbery DM, Huls G, Furlong T, Myerson D, Loeb KR, Fann JR, Castilla-Llorente C, McDonald GB, Martin PJ. Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease. PLoS One. 2017 Aug 17;12(8):e0183284. doi: 10.1371/journal.pone.0183284. eCollection 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Martin principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing lithium carbonate and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Recovery (time frame: at 28 days after starting treatment with the study product). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00408681, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017.