A Multi-Center Study of Nonmyeloablative Conditioning With TBI or Fludarabine/TBI for HLA-matched Related Hematopoietic Cell Transplantation for Treatment of Hematologic Malignancies With Post Grafting Immunosuppression With Tacrolimus and Mycophenolate Mofetil
fludarabine phosphate
+ total-body irradiation
+ laboratory biomarker analysis
Plasmablastic Lymphoma+83
+ Lymphadenopathy
+ Bacterial Infections and Mycoses
Treatment Study
Summary
Study start date: April 1, 2004
Actual date on which the first participant was enrolled.PRIMARY OBJECTIVES: I. To estimate the incidence of grade III/IV graft-versus-host disease (GVHD) after conditioning with 200 centigray (cGy) TBI alone or Fludarabine (fludarabine phosphate)/200 cGy TBI followed by tacrolimus (Tac)/mycophenolate mofetil (MMF) immunosuppression in patients with hematologic malignancies. II. To estimate the incidence of chronic extensive GVHD. SECONDARY OBJECTIVES: I. To estimate the incidences of graft rejection. II. To estimate overall survival 1-year after conditioning. III. To evaluate the incidences of grades II-IV acute GVHD. IV. To evaluate the rates of disease progression and/or relapse-related mortality. V. To estimate the rate and duration of steroid use for the treatment of chronic GVHD. OUTLINE: Patients are assigned to 1 of 2 treatment arms. ARM I (nonmyeloablative conditioning with fludarabine phosphate and TBI): Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0. ARM II (nonmyeloablative conditioning with TBI): Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus orally (PO) every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.150 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Until 74 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: * Patient must be not eligible for conventional allogeneic hematopoietic cell transplantation (HCT) and must have disease expected to be stable for at least 100 days without chemotherapy; patients with hematologic malignancies treatable with HCT or with a B cell malignancy except those curable with autologous transplant will be included; patients not eligible for active disease specific protocols may be enrolled in this protocol; patients will include the following * Diffuse large B cell non-Hodgkin lymphoma (NHL) and other aggressive lymphomas - not eligible for conventional myeloablative HCT or after autologous HCT * Low grade NHL- with \< 6 months duration of complete response (CR) between courses of conventional therapy * Mantle cell NHL- may be treated in first CR * Chronic lymphocytic leukemia (CLL) - must have either 1) failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine phosphate (FLU) (or another nucleoside analog, e.g. 2-chlorodeoxyadenosine \[2-CDA\], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; or 3) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or a diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL * Hodgkin lymphoma (HL) - must have received and failed frontline therapy; patients must have failed or were not eligible for autologous transplant * Multiple myeloma (MM) - following a planned autologous transplant or equivalent high-dose therapy without a graft, or following a failed prior autograft * Acute myeloid leukemia (AML) - must have \< 5% marrow blasts at the time of transplant * Acute lymphoblastic leukemia (ALL) - must have \< 5% marrow blasts at the time of transplant * Chronic myelogenous leukemia (CML) - patients will be accepted beyond first chronic phase (CP1) if they have received previous myelosuppressive chemotherapy or HCT, and have \< 5% marrow blasts at time of transplant * Myelodysplastic syndromes/myeloproliferative disorders (MDS/MPD) - must have received previous myelosuppressive chemotherapy or HCT, and have \< 5% marrow blasts at time of transplant * Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy * Myelosuppressive chemotherapy must be discontinued three weeks prior to conditioning with the exception of hydroxyurea or imatinib * Patients \< 12 years old must be approved by both the participating institutions' patient review committee such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and the FHCRC principal investigator * Patient who refused to be treated on a conventional HCT protocol; for this inclusion criterion, 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 investigators * Patients with human leukocyte antigen (HLA)-matched related donors * Patients with renal failure are eligible; however, patients with renal compromise (serum creatinine \> 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum tacrolimus levels * DONOR: Related donor who is HLA genotypically identical at least at one haplotype and may be phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1 * DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis * DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian) Exclusion Criteria: * Eligible for a high priority curative autologous transplant * Patient with rapidly progressive, aggressive NHL unless in minimal disease state * Patients with chronic myelomonocytic leukemia (CMML) * Life expectancy severely limited by diseases other than malignancy * Any current central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy * Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML * Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment * Female patients who are pregnant or breastfeeding * Human immunodeficiency virus (HIV)-positive patients * Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy * 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; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy * Fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month * Karnofsky score \< 50 for adult patients * Lansky-Play performance score \< 50 for pediatric patients * Symptomatic coronary artery disease or ejection fraction \< 35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of \< 26%); ejection fraction is required if age \> 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction \< 26% may be enrolled if approved by a cardiologist * Poorly controlled hypertension * Diffusing capacity of the lung for carbon monoxide (DLCO) \< 30%, total lung capacity (TLC) \< 30%, forced expiratory volume in one second (FEV1) \< 30% and/or receiving supplementary continuous oxygen; the FHCRC principal investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules * Liver function abnormalities: 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, 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 or bridging fibrosis, 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, and symptomatic biliary disease * Patients with active bacterial or fungal infections unresponsive to medical therapy * DONOR: Age less than 12 years * DONOR: Identical twin * DONOR: Pregnancy * DONOR: Infection with HIV * DONOR: Known allergy to filgrastim (G-CSF) * DONOR: Current serious systemic illness that would result in increased risk for G-CSF mobilization and harvest of peripheral blood stem cells (PBSC)
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.2 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 5 locations
LDS Hospital
Salt Lake City, United StatesVA Puget Sound Health Care System
Seattle, United StatesFred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, United States