Clinical trial NCT00410657: Alemtuzumab and Glucocorticoids in Treating Newly Diagnosed Acute Graft-Versus-Host Disease in Patients Who Have Undergone a Donor Stem Cell Transplant
Official title: A Phase II Study to Evaluate Low-Dose Alemtuzumab as a Glucocorticoid-Sparing Agent for Initial Systemic Treatment of Acute Graft-Versus-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
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)
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis
chronic myelomonocytic leukemia
chronic neutrophilic leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
juvenile myelomonocytic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
stage III grade 1 follicular lymphoma
stage IV grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
stage III grade 2 follicular lymphoma
stage IV grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
splenic marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
poor prognosis metastatic gestational trophoblastic tumor
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
aggressive, noncontiguous stage II adult non-Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
stage III malignant testicular germ cell tumor
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood myelodysplastic syndromes
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-12-13
Enrollment: 53
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Alemtuzumab and glucocorticoids, such as prednisone or methylprednisolone, may be an effective treatment for acute graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This phase II trial is studying how well giving alemtuzumab together with glucocorticoids works in treating newly diagnosed acute graft-versus-host disease in patients who have undergone donor stem cell transplant.

Detailed description: OBJECTIVES:

* Determine whether the administration of low-dose alemtuzumab at the onset of acute graft-versus-host disease can accelerate withdrawal of glucocorticoids and decrease nonrelapsing mortality in patients who have undergone myeloablative allogeneic stem cell transplantation.

OUTLINE: This is an open-label, nonrandomized study.

Within 72 hours of beginning glucocorticoid therapy, patients receive alemtuzumab IV over at least 2 hours on days 1 and 2. If graft-versus-host disease (GVHD) responds well during days 1-14 but returns between days 28 and 56, patients are eligible to receive 2 additional doses of alemtuzumab.

Patients receive glucocorticoid therapy comprising methylprednisolone IV or oral prednisone daily until objective evidence of improvement in manifestations of GVHD. Patients with resolved or significantly improved GVHD receive treatment until day 10 followed by an accelerated taper until day 72 if no flare up of GVHD occurs during the glucocorticoid taper. Patients with recurrent or progressive GVHD during the accelerated taper are treated for 5-7 days before resuming a less rapid taper. Patients with no improvement may receive secondary therapy with alternative immunosuppressive medications at the discretion of the managing physician. Treatment continues in the absence of progressive GVHD of at least 3 days duration during days 2-10; persisting GVHD without improvement between days 10-14; recurrent or progressive GVHD after day 10 that does not respond within 3 days to topical immunosuppressive therapy; and/or an increase in the systemic glucocorticoid dose by two taper steps; or unacceptable toxicity.

Patients undergo blood collection at baseline and then periodically during study treatment for pharmacokinetics and quantification of viral loads for human herpes virus 6, adenovirus, Epstein-Barr virus, and cytomegalovirus. Samples are also examined by flow cytometry for B- and T-cell quantification at baseline, periodically during study treatment, and at 1 year after transplantation.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Newly diagnosed acute graft-versus-host disease (GVHD)

  * Grade IIB-IV disease
* Requires glucocorticoids for treatment of GVHD, as indicated by 1 of the following:

  * Initial treatment with prednisone or methylprednisolone at 2 mg/kg is indicated (in the judgement of the attending physician) by any of the following:

    * Severity of GVHD requires hospitalization
    * GVHD manifestations include symptoms other than anorexia, nausea, and vomiting
    * GVHD begins within 2-3 weeks after hematopoietic stem cell transplantation (HSCT)
    * GVHD manifestations progress rapidly from 1 day to the next before treatment
  * Initial treatment with prednisone or methylprednisolone at 1 mg/kg did not produce adequate clinical improvement within the first 4 days (in the judgement of the attending physician)
* Has undergone allogeneic HSCT with myeloablative conditioning

  * No nonmyeloablative conditioning or autologous HSCT
* No primary treatment of acute GVHD with methylprednisolone at any of the following doses:

  * More than 2 mg/kg/day at any time
  * 2 mg/kg/day for \> 72 hours
  * 1 mg/kg/day for \> 96 hours
* No presence of distinctive or diagnostic manifestations of chronic GVHD
* No relapsed, refractory, or secondary malignancy

PATIENT CHARACTERISTICS:

* Karnofsky performance status (PS) 20-100% OR Lanksy PS 20-100%
* Life expectancy ≥ 1 month
* Absolute neutrophil count ≥ 500/mm\^3
* Negative pregnancy test
* No Mini Mental State Exam score \< 24/30 or confusion (for patients \> 12 years of age)
* No history of type I hypersensitivity reaction to alemtuzumab or any of its components
* No increasing levels of viremia by serial quantitative viral plasma polymerase chain reaction assays
* No invasive viral or fungal disease that does not respond to appropriate antiviral or antifungal medications

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No systemic immunosuppression tapered or stopped for treatment of leukemic relapse or minimal residual disease

Primary outcomes:
measure: Proportion of patients with methylprednisolone (MP)-equivalent glucocorticoid doses ≤ 0.75 mg/kg on day 28 after starting therapy for graft-versus-host disease (GVHD)
Secondary outcomes:
measure: Total cumulative dose of MP-equivalent treatment during the first 8 weeks after study entry
measure: Proportion of patients with complete response, measured weekly through day 56
measure: Incidence of secondary systemic therapy for acute GVHD
measure: Cumulative acute GVHD activity index score at day 56
measure: Incidence of chronic GVHD at 1 year
measure: Nonrelapsing mortality at 1 year
measure: Survival at 1 year
measure: Cumulative incidence of opportunistic infections at 1 year
measure: Cumulative incidence of recurrent or progressive malignancy at 1 year
measure: Peripheral blood CD4, CD8, CD19, and CD16/56 counts at baseline and then periodically for 1 year
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Paul Carpenter, MD
role: PRINCIPAL_INVESTIGATOR
References: