Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies

Completed · Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID: NCT00040846
Run by: Fred Hutchinson Cancer Center
People needed: 60
Starts: 2001-11-01
Expected to finish: 2009-12-01
Last updated by the study team: 2020-01-29

Who can join

Age: any, up to 74. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy; patients with hematologic malignancies treatable with hematopoietic stem cell transplant (HSCT) or with a B cell malignancy except those treatable with autologous transplant will be included
Aggressive non-Hodgkin lymphomas (NHLs) and Other Histologies Such as Diffuse large B cell NHL
Patients with primary refractory or relapsed disease not eligible for an autologous transplant
Patients are eligible following an autologous transplant in remission or in relapse
Planned tandem transplant is allowed for patients at high risk of relapse
Low grade NHL with < 6 months duration of complete remission (CR) between courses of conventional therapy
Mantle Cell NHL may be treated in first CR
Chronic lymphocytic leukemia (CLL) - Must have failed 2 lines of conventional therapy and be refractory to fludarabine
Hodgkin disease (HD) - Must have received and failed frontline therapy; patients must have had a prior autologous transplant or were not eligible for autologous transplant; planned tandem transplants are allowed for patients at high risk of relapse
Multiple myeloma (MM) - Must have received prior chemotherapy and a prior autologous transplant, unless autologous transplant was not possible; planned tandem transplants are allowed for patients at high risk of relapse
Acute myeloid leukemia (AML) - Must have < 5% marrow blasts at the time of transplant
Acute lymphocytic leukemia (ALL) - Must have < 5% blasts at the time of transplant
Chronic myeloid leukemia (CML) - Patients will be accepted beyond chronic phase 1 (CP1) if they have received previous myelosuppressive chemotherapy or HSCT, and have < 5% marrow blasts at time of transplant
Myelodysplastic (MDS)/Myeloproliferative disorders - Must have failed previous myelosuppressive chemotherapy or HSCT, and have < 5% marrow blasts at time of transplant
Waldenstrom's Macroglobulinemia - Must have failed 2 courses of therapy
Patients < 12 years old must be approved by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI)
Patients who refuse to be treated on a conventional transplant protocol; for this inclusion, criteria transplants must be approved by both the participating institution´s patient review committee such as the Patient Care Conference (PCC) at the FHCRC and the FHCRC principal investigator
Patients with related or unrelated donors for whom
The best available match is a HLA class II DRB1 and DQB1 matched donor incompatible for any single serologically detectable class I HLA-A, -B, -C mismatch; one additional allele level class I mismatch is allowed OR any combination of 2 allele level mismatches (if typed at the molecular level)
There is a likelihood of rapid disease progression while HLA typing and results of a preliminary search and the donor pool suggests that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found
There is no HLA-A, -B or -C one locus allelic mismatched related donor available
There is no indication for an autologous transplantation as a treatment option
DONOR: Related or unrelated donors who are matched for HLA-DRB1 and DQB1 alleles (must be defined by high resolution typing), and who are mismatched for:
Any single serologically detectable HLA-A or B or C antigen +/- 1 allele or
Any combination of two HLA-A, -B, or -C alleles (if prospectively typed at molecular level)

You may not qualify if…

Patients who are homozygous at the mismatched major histocompatibility complex (MHC) class I locus
A positive cross-match exists between the donor and recipient
Patients with rapidly progressive intermediate or high grade NHL
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
Life expectancy severely limited by diseases other than malignancy
Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment
Female patients who are pregnant or breast-feeding
Human immunodeficiency virus (HIV) positive patients
Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
Patients with active bacterial or fungal infections unresponsive to medical therapy
Patients with the following organ dysfunction symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy; ejection fraction is required if the patient is > 50 years of age, or history of cardiac disease or anthracycline exposure
Diffusion capacity of carbon monoxide (DLCO) < 35%; total lung capacity (TLC) < 35%; or forced expiratory volume in one second (FEV1) < 35% and/or receiving supplementary continuous oxygen
Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure; cirrhosis of the liver with evidence of portal hypertension; alcoholic hepatitis; esophageal varices; a history of bleeding esophageal varices; hepatic encephalopathy; uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time; ascites related to portal hypertension; bacterial or fungal liver abscess; biliary obstruction; chronic viral hepatitis with total serum bilirubin >3 mg/dL; or symptomatic biliary disease
Patients with poorly controlled hypertension on multiple antihypertensives
Karnofsky score < 70 for adult patients
Lansky-Play Performance Score < 50 for pediatric patients
DONOR: Bone marrow (BM) donors
DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for granulocyte colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem cell (PBSC)
DONOR: Donors < 12 years of age

Where it is running

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

Full record on ClinicalTrials.gov

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