Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
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.
Acute Undifferentiated Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Myelomonocytic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Juvenile Myelomonocytic Leukemia
Mast Cell Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
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 Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Relapsing Chronic Myelogenous Leukemia
Secondary Myelodysplastic Syndromes
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Radiation: total-body irradiation
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Biological: graft versus host disease prophylaxis/therapy
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Campath (Alemtuzumab) Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class II Mismatched Donor Stem Cell Transplantation for Patients With Hematologic Malignancies: A Multicenter Trial|
- Dose of alemtuzumab that allows an incidence of grade III-IV acute GVHD less than 40% [ Time Frame: Day +100 ] [ Designated as safety issue: Yes ]
- Graft rejection [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
- Number of days of steroids greater than 1 mg/kg required in each patient [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Non-relapse mortality [ Time Frame: Day +100 ] [ Designated as safety issue: Yes ]
- Infection [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Immune reconstitution [ Time Frame: Up to 1 year post-transplant ] [ Designated as safety issue: No ]
- Disease progression/relapse [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||March 2005|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy, TBI, transplant)
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab 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 TBI on day 0.
ALLOGENEIC PBSCT: After completion of TBI, patients undergo allogeneic PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine 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.
Other Names:Radiation: total-body irradiation
Undergo low-dose TBI
Other Name: TBIDrug: fludarabine phosphate
Other Names:Drug: cyclosporine
Given PO or IV
Other Names:Drug: mycophenolate mofetil
Other Names:Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic stem cell transplantationProcedure: peripheral blood stem cell transplantation
Other Names:Biological: graft versus host disease prophylaxis/therapy
Undergo GVHD prophylaxis/therapy
Other Names:Other: laboratory biomarker analysis
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%.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00118352
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|University of Torino|
|Torino, Italy, 10126|
|Principal Investigator:||Brenda Sandmaier||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|