Clinical trial NCT00109993: Campath-1H + FK506 and Methylprednisolone for GVHD
Official title: Phase II Clinical Trial Incorporating Alemtuzumab (Campath-1H) in Combination With FK506 and Methylprednisolone for Treatment of Severe Acute Graft vs Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Keywords: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-05-04
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Graft-vs-host disease response
timeFrame: 1, 2, 3, and 4 months
Secondary outcomes:
measure: Incidence of serious infections by clinical, radiologic, and microbiologic assessments
timeFrame: 1,2,3, and 4 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
Study officials:
affiliation: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
name: Mary Laughlin, MD
role: PRINCIPAL_INVESTIGATOR
References: