Clinical trial NCT00040846
Conditions: Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) 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) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Contiguous Stage II Grade 1 Follicular Lymphoma Contiguous Stage II Grade 2 Follicular Lymphoma Contiguous Stage II Marginal Zone Lymphoma Contiguous Stage II Small Lymphocytic Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Peripheral T-cell Lymphoma Previously Treated Myelodysplastic Syndromes Progressive Hairy Cell Leukemia, Initial Treatment 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 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 Splenic Marginal Zone Lymphoma Stage I Adult Diffuse Small Cleaved Cell Lymphoma Stage I Childhood Anaplastic Large Cell Lymphoma Stage I Childhood Large Cell Lymphoma Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Mycosis Fungoides/Sezary Syndrome Stage I Small Lymphocytic Lymphoma Stage II Childhood Anaplastic Large Cell Lymphoma Stage II Childhood Large Cell Lymphoma Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Mycosis Fungoides/Sezary Syndrome Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Childhood Anaplastic Large Cell Lymphoma Stage III Childhood Large Cell Lymphoma Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Mycosis Fungoides/Sezary Syndrome Stage III Small Lymphocytic Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Childhood Anaplastic Large Cell Lymphoma Stage IV Childhood Large Cell Lymphoma Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma T-cell Large Granular Lymphocyte Leukemia Waldenström Macroglobulinemia
Sponsor: Fred Hutchinson Cancer Center
Start date: 2001-11-01; Completion date: 2009-12-01
Enrollment: 60 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: CONDITIONING REGIMEN: Patients receive alemtuzumab 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.

HSCT: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive CSP IV or PO BID on days -3 to 180 with taper to day 365 and MMF PO TID on days 0-100, with taper to day 156.
Interventions: intervention 1: alemtuzumab intervention 2: fludarabine phosphate intervention 3: total-body irradiation intervention 4: allogeneic hematopoietic stem cell transplantation intervention 5: peripheral blood stem cell transplantation intervention 6: mycophenolate mofetil intervention 7: cyclosporine
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Undergo TBI intervention 4: Undergo allogeneic HSCT intervention 5: Undergo allogeneic peripheral blood stem cell transplantation intervention 6: Given PO intervention 7: Given IV or PO

Protocol documents: