This phase II trial is studying the side effects and best dose of alemtuzumab when given together with fludarabine phosphate and total-body irradiation followed by cyclosporine and mycophenolate mofetil in treating patients who are undergoing a donor stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, a monoclonal antibody, such as alemtuzumab, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PRIMARY OBJECTIVES: I. To determine which dose of Campath (alemtuzumab) allows related and unrelated human leukocyte antigen (HLA) class-II mismatched hematopoietic cell transplantation (HCT) with an incidence of grade III-IV acute graft-versus-host disease (GVHD) less than 40%. SECONDARY OBJECTIVES: I. Incidence of graft rejection. II. Number of days of steroids \>= 1mg/kg required before day 100 in each patient. III. Incidence of non-relapse mortality. IV. Risk/incidence of infections. V. Immune reconstitution. VI. Risk for disease progression and relapse. OUTLINE: This is a dose-escalation study of alemtuzumab. NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab intravenously (IV) over 6 hours once daily on days -6, -5, and -4 OR days -5 and -4 and fludarabine phosphate IV over 30 minutes on days -4, -3, and -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0. ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): After completion of TBI, patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV every 12 hours on days -3 to 180 followed by a taper until day 365 in the absence of GVHD. Beginning 4-6 hours after completion of allogeneic PBSCT, patients receive mycophenolate mofetil PO every 8 hours on days 0 to 100 followed by a taper until day 156 in the absence of GVHD. After completion of study treatment, patients are followed up periodically for 12 months, at 18 months, and then annually for 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Given IV
Undergo low-dose TBI
Given IV
Given PO or IV
Given PO
Undergo allogeneic stem cell transplantation
Undergo PBSCT
Undergo GVHD prophylaxis/therapy
Correlative studies
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
University of Torino
Torino, Italy
Incidence of Grade III-IV Acute GVHD
Severity of Individual Organ Involvement Liver: Stage 2 - bilirubin (3-5.9mg/100ml) Stage 3 - bilirubin (6-14.9mg/100ml) Stage 4 - bilirubin \> 15mg/100ml Gut: Diarrhea is graded stage 1 to stage 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as stage 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 Severity of GVHD Grade III - Stage 2 to 4 gastrointestinal involvement and/or Stage 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: 100 days after transplant
Incidence of Graft Rejection
Percentage patients that experienced graft rejection.
Time frame: 84 days after transplant
Incidence of High-dose Corticosteroid Utilization.
Percentage patients requiring steroids greater than 1 mg/kg.
Time frame: 100 days after transplant
Incidence of Non-relapse Mortality
Percentage patient deaths due to non-relapse mortality
Time frame: 100 days after transplant
Incidence of Infection
Percentage patients that experienced infection(s).
Time frame: Up to 5 years post-transplant
Immune Reconstitution
The outcome of immune reconstitution was not analyzed by the collaborating laboratory because only a small number of patients were only enrolled in Dose Level 1 (no alemtuzumab). The Dose Level 1 patients were going to be the baseline for which to compare the other patients on Dose Level 2 (and 3) who would have received alemtuzumab. The collaborating investigator determined that the study was not worthwhile performing based on this information.
Time frame: Up to 1 year post-transplant
Disease Progression/Relapse
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever greater than 38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes \>20%. AML, ALL \>5% marrow blasts by morphologic or flow cytometric, or appearance of extramedullary disease. CLL ≥1 of: Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL \>25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
Time frame: Up to 5 years
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