Clinical trial NCT00408681: Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease (GVHD) After Donor Stem Cell Transplant
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Atypical Chronic Myeloid Leukemia, Breakpoint Cluster Region-abl Translocation (BCR-ABL) Negative
Blastic Phase Chronic Myelogenous Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Childhood Myelodysplastic Syndromes
Chronic Eosinophilic Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
de Novo Myelodysplastic Syndromes
Disseminated Neuroblastoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Gastrointestinal Complications
Juvenile Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Poor Prognosis Metastatic Gestational Trophoblastic Tumor
Previously Treated Childhood Rhabdomyosarcoma
Primary Myelofibrosis
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Malignant Testicular Germ Cell Tumor
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Neuroblastoma
Recurrent Ovarian Epithelial Cancer
Recurrent Ovarian Germ Cell Tumor
Recurrent Small Lymphocytic Lymphoma
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Splenic Marginal Zone Lymphoma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage II Ovarian Epithelial Cancer
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Malignant Testicular Germ Cell Tumor
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage III Ovarian Epithelial Cancer
Stage III Small Lymphocytic Lymphoma
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Breast Cancer
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Ovarian Epithelial Cancer
Stage IV Small Lymphocytic Lymphoma
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-12-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Functional Recovery
timeFrame: at 28 days after starting treatment with the study product
Secondary outcomes:
measure: Duration of Treatment With the Study Product
timeFrame: Up to 6 months
measure: Mucosal Anatomic Recovery
timeFrame: 2 to 3 weeks after starting treatment with the study product
measure: Mucosal Anatomic Recovery
timeFrame: 4 weeks after starting treatment with the study product
measure: Mucosal Anatomic Recovery
timeFrame: 5 weeks after starting treatment with the study product
measure: Mucosal Anatomic Recovery
timeFrame: 6 to 7 weeks after starting treatment with the study product
measure: Mucosal Anatomic Recovery
timeFrame: 9 to 11 weeks after starting treatment with the study product
measure: Recurrent or Progressive Malignancy
timeFrame: 2 years after enrollment
measure: Non-relapse Mortality
timeFrame: 2 years after enrollment
measure: Survival
timeFrame: 6 months after enrollment
measure: Survival
timeFrame: 1 year after enrollment
measure: Survival
timeFrame: 2 years after enrollment
measure: Causes of Death
timeFrame: up to 6 years after enrollment
Other outcomes:
measure: Agents Added to Treat GVHD More Than 3 Days After Enrollment
timeFrame: Up to 100 days after enrollment
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Paul Martin
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.