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

Fred Hutchinson Cancer Center (FHCC)

Status: Completed

Conditions: Stage IIIA Breast Cancer; Stage III Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Chronic Neutrophilic Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Recurrent Ovarian Germ Cell Tumor; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Childhood Myelodysplastic Syndromes; Stage III Grade 3 Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Stage I Multiple Myeloma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Chronic Myelomonocytic Leukemia; Childhood Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Stage III Adult Diffuse Large Cell Lymphoma; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Ovarian Epithelial Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Stage III Multiple Myeloma; Stage III Marginal Zone Lymphoma; Refractory Hairy Cell Leukemia; Recurrent Childhood Rhabdomyosarcoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Ovarian Epithelial Cancer; Stage IV Adult Hodgkin Lymphoma; Stage IIIB Breast Cancer; Stage III Ovarian Epithelial Cancer; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Stage IV Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Secondary Myelodysplastic Syndromes; Disseminated Neuroblastoma; Stage IV Adult Burkitt Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage II Ovarian Epithelial Cancer; Recurrent Adult Acute Myeloid Leukemia; Stage II Multiple Myeloma; Stage IV Small Lymphocytic Lymphoma; Recurrent Neuroblastoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Splenic Marginal Zone Lymphoma; Chronic Eosinophilic Leukemia; Noncontiguous Stage II Marginal Zone Lymphoma; Adult Acute Myeloid Leukemia in Remission; Stage IV Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Adult Immunoblastic Large Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Stage III Adult Hodgkin Lymphoma; Juvenile Myelomonocytic Leukemia; Stage III Adult Lymphoblastic Lymphoma; Gastrointestinal Complications; Accelerated Phase Chronic Myelogenous Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Noncontiguous Stage II Adult Burkitt Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Recurrent Childhood Small Noncleaved Cell Lymphoma; Previously Treated Childhood Rhabdomyosarcoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Recurrent Adult Hodgkin Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Recurrent Adult Diffuse Mixed Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage IIIC Breast Cancer; Stage IV Grade 3 Follicular Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Malignant Testicular Germ Cell Tumor; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Adult Acute Lymphoblastic Leukemia in Remission; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Childhood Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Noncontiguous Stage II Grade 3 Follicular Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Stage IV Mantle Cell Lymphoma; Primary Myelofibrosis; Secondary Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Atypical Chronic Myeloid Leukemia, Breakpoint Cluster Region-abl Translocation (BCR-ABL) Negative; Stage IV Grade 1 Follicular Lymphoma; Stage IV Breast Cancer

Treatments: Drug: lithium carbonate; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00408681

2080.00

NCI-2010-00269

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Other: laboratory biomarker analysis

Drug: lithium carbonate