Campath-1H + FK506 and Methylprednisolone for GVHD

Study Overview
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Brief Summary
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RATIONALE: Alemtuzumab, tacrolimus, and methylprednisolone may be an effective treatment for graft-versus-host disease caused by a donor stem cell transplant. PURPOSE: This phase II trial is studying how well giving alemtuzumab together with tacrolimus and methylprednisolone works in treating acute graft-versus-host disease in patients who have undergone donor stem cell transplant.

Detailed Description
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OBJECTIVES: Primary Determine the 4-week rate of complete response in patients with severe acute graft-vs-host disease (GVHD) treated with alemtuzumab, tacrolimus, and methylprednisolone within 100 days after undergoing allogeneic stem cell transplantation. Secondary Determine the best response at 4 and 12 weeks in patients treated with this regimen. Determine 6-month survival of patients treated with this regimen. Determine the rate of infectious complications in patients treated with this regimen. Determine rate of chronic GVHD in patients treated with this regimen. OUTLINE: This is an open-label, single-blind, multicenter study. Patients receive methylprednisolone IV on days 1-3 and then orally or IV on days 4-14; tacrolimus IV continuously on days 1-7 and then orally once or twice daily on days 8-180, followed by a taper in the absence of chronic graft-vs-host disease; and alemtuzumab IV over 2 hours on days 4-6, 18, and 32. Treatment continues in the absence of unacceptable toxicity or the development of serious infection. After completion of study treatment, patients are followed at 2 and 4 weeks. PROJECTED ACCRUAL: A total of 9-34 patients will be accrued for this study within 8-12 months.

Official Title
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Phase II Clinical Trial Incorporating Alemtuzumab (Campath-1H) in Combination With FK506 and Methylprednisolone for Treatment of Severe Acute Graft vs Host Disease

Conditions
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Breast Cancer, Chronic Myeloproliferative Disorders, Gestational Trophoblastic Tumor, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases, Neuroblastoma, Ovarian Cancer, Testicular Germ Cell Tumor

Intervention / Treatment
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* Biological: alemtuzumab
* Drug: methylprednisolone
* Drug: tacrolimus


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of acute graft-vs-host disease (GVHD) Clinical grade C or D disease No grade C disease with single organ skin involvement Has undergone allogeneic stem cell transplantation within the past 100 days Absolute neutrophil count > 500/mm^3 (donor-derived [> 60% by peripheral blood lymphocyte chimerism analyses]) No development of GVHD after prior donor lymphocyte infusion Must have received prior prophylactic cyclosporine or tacrolimus at the onset of acute GVHD PATIENT CHARACTERISTICS: Age Over 18 Performance status Not specified Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic No serologic evidence of active hepatitis B or C infection Renal Creatinine ≤ 3.5 mg/dL No requirement for dialysis Cardiovascular No requirement for vasopressors Pulmonary No requirement for a ventilator Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study treatment No known HIV positivity No active uncontrolled infection No other organ dysfunction PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: alemtuzumab|alemtuzumab IV over 2 hours on days 4-6, 18, and 32|
|Drug: methylprednisolone|methylprednisolone IV on days 1-3 and then orally or IV on days 4-14|
|Drug: tacrolimus|tacrolimus IV continuously on days 1-7 and then orally once or twice daily on days 8-180, followed by a taper in the absence of chronic graft-vs-host disease|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft-vs-host disease response |  | 1, 2, 3, and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious infections by clinical, radiologic, and microbiologic assessments |  | 1,2,3, and 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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graft versus host disease, 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, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, chronic idiopathic myelofibrosis, 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, myelodysplastic/myeloproliferative disease, 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 myelodysplastic syndromes, 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 grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mantle cell lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, recurrent neuroblastoma, recurrent ovarian epithelial cancer, recurrent ovarian germ cell tumor, recurrent small lymphocytic lymphoma, recurrent malignant testicular germ cell tumor, refractory chronic lymphocytic leukemia, refractory multiple myeloma, refractory hairy cell leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, splenic marginal zone lymphoma, stage I multiple myeloma, 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 immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage II ovarian epithelial cancer, 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 mantle cell lymphoma, stage III marginal zone lymphoma, stage III multiple myeloma, stage III ovarian epithelial cancer, stage III small lymphocytic lymphoma, stage III malignant testicular germ cell tumor, 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 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