This phase II trial studies the side effects and the best dose of alemtuzumab when given together with fludarabine phosphate and low-dose total body irradiation (TBI) and how well it works before donor stem cell transplant in treating patients with hematological malignancies. Giving chemotherapy and low-dose TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF) after transplant may stop this from happening.
PRIMARY OBJECTIVES: I. To determine whether stable allogeneic engraftment from related and unrelated human leukocyte antigen (HLA)-mismatched stem cell donors can be safely established using a non-myeloablative conditioning regimen plus escalating doses of the anti-CD52 monoclonal antibody (mAb) Campath (alemtuzumab) in patients with hematologic malignancies. SECONDARY OBJECTIVES: I. Evaluate the risk of occurrence of acute and chronic graft-vs-host disease (GVHD). II. Evaluate the risk/incidence of infections. III. Determine whether engraftment can be maintained with a single dose fludarabine, donor lymphocyte infusion (DLI) and continued MMF/CSP. IV. Evaluate the risk for disease progression and relapse. OUTLINE: This is a dose-escalation study of alemtuzumab. CONDITIONING REGIMEN: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -5 and fludarabine phosphate IV on days -4 to -2. Patients also undergo low-dose TBI on day 0. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. IMMUNOSUPPRESSION: Patients receive CSP IV or orally (PO) twice daily (BID) on days -3 to 180 with taper to day 365 and MMF PO thrice daily (TID) on days 0-100 with taper to day 156. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Given IV
Given IV
Undergo TBI
Undergo allogeneic HSCT
Undergo allogeneic peripheral blood stem cell transplantation
Given PO
Given IV or PO
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
LDS Hospital
Salt Lake City, Utah, United States
VA Puget Sound Health Care System
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Froedtert Memorial Lutheran Hospital, Medical College of Wisconsin
Milwaukee, Wisconsin, United States
University of Torino
Torino, Italy
Evaluate the Risk of Transplant Related Mortality.
Percentage patients with Day 100 transplant related mortality.
Time frame: 100 days after transplant
Evaluate the Risk of Occurrence of Acute and Chronic GVHD
Percentage patients who developed acute/chronic GVHD. aGVHD Stages Skin: 1. a maculopapular eruption involving \< 25% BSA 2. a maculopapular eruption involving 25 - 50% BSA 3. generalized erythroderma 4. generalized erythroderma with bullous formation and often with desquamation Liver: 1. bilirubin 2.0 - 3.0 mg/100 mL 2. bilirubin 3 - 5.9 mg/100 mL 3. bilirubin 6 - 14.9 mg/100 mL 4. bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gastrointestinal involvement and/or +2 to +4 liver involvement, with or without a rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
Time frame: 1 year after transplant
Determine Whether Engraftment Can be Maintained With a Single Dose Fludarabine, DLI and Continued MMF/CSP, Defined as Rejection Rate < 20%.
Mixed chimerism will be defined as the detection of donor T cells (CD3+) and granulocytes (CD 33+), as a proportion of the total T cell and granulocyte population, respectively, of greater than 5% and less than 95% in the peripheral blood. Full donor chimerism is defined as \> 95% donor CD3+ T cells.
Time frame: 100 days after transplant
Evaluate the Risk/Incidence of Infections
Percentage patients who experienced infections within 100 days post-transplant.
Time frame: 100 days after transplant
Evaluate the Risk for Disease Progression and Relapse
Percentage patients who relapsed/progressed within 1 year post-transplant.
Time frame: 1 year after transplant
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