Non Hodgkin Lymphoma Clinical Trial

Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

Summary

This phase I/II trial studies whether a new kind of blood stem cell (bone marrow) transplant, that may be less toxic, is able to treat underlying blood cancer. Stem cells are "seed cells" necessary to make blood cells. Researchers want to see if using less radiation and less chemotherapy with new immune suppressing drugs will enable a stem cell transplant to work. Researchers are hoping to see a mixture of recipient and donor stem cells after transplant. This mixture of donor and recipient stem cells is called "mixed-chimerism". Researchers hope to see these donor cells eliminate tumor cells. This is called a "graft-versus-leukemia" response.

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Full Description

PRIMARY OBJECTIVES:

I. To determine whether stable unrelated peripheral blood stem cell (PBSC) grafts can be safely established using nonmyeloablative pretransplant conditioning with intensified post-grafting immunosuppression and with every (q) 8 hours (hr) and possibly q 6 hr mycophenolate mofetil (MMF) dosing in patients with hematologic malignancies and renal cell carcinoma.

II. To determine if the incidence and severity of acute grades II-IV graft-versus-host disease (GVHD) can be reduced in patients with sustained engraftment with the use of q 8 hr MMF dosing.

SECONDARY OBJECTIVES:

I. To determine if engraftment can be maintained in patients with low chimerism and high risk of rejection with the use of a single dose of fludarabine (fludarabine phosphate) followed by donor lymphocyte infusion (DLI) on continued MMF/cyclosporine (CSP).

II. To compare survival and disease free survival to those achieved under protocol 1463.

OUTLINE:

REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4, -3, and -2 and undergo total-body irradiation (TBI) on day 0.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO every 8 hours on days 0-40 with taper to day 96.

After completion of study treatment, patients are followed up at 6 months, 1 year, 1.5 years, 2 years, and then annually thereafter.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Ages > 50 years with hematologic malignancies treatable by unrelated hematopoietic stem cell transplantation (HSCT)
Ages =< 50 years of age with hematologic diseases treatable by allogeneic HSCT who through pre-existing medical conditions or prior therapy are considered to be at high risk for regimen related toxicity associated with a conventional transplant (> 40% risk of transplant related mortality [TRM]) or those patients who refuse a conventional HSCT; transplants must be approved for these inclusion criteria by both the participating institution's patient review committee such as the Patient Care Conference (PCC at the Fred Hutchinson Cancer Research Center [FHCRC]) and by the principal investigator at the collaborating center; patients =< 50 years of age who have received previous autologous transplantation do not require patient review committee approval; all children < 12 years must be discussed with the FHCRC principal investigator (PI) prior to registration
Patients with metastatic renal cell carcinoma with the histologic subtypes of clear cell, papillary and medullary may be accepted regardless of age

The following diseases will be permitted although other diagnoses can be considered if approved by PCC or the participating institution's patient review committees and the principal investigator:

Intermediate or high grade non-Hodgkin lymphoma (NHL) - not eligible for autologous HSCT or after failed autologous HSCT
Low grade NHL - with < 6 month duration of complete remission (CR) between courses of conventional therapy
Chronic lymphocytic leukemia (CLL) - must have failed two lines of conventional therapy and be refractory to fludarabine
Hodgkin's disease (HD) - must have received and failed frontline therapy
Multiple myeloma (MM) - must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT is permitted
Acute myeloid leukemia (AML) - must have < 5% marrow blasts at the time of transplant
Acute lymphoblastic leukemia - must have < 5% blasts at the time of transplant
Chronic myelogenous leukemia (CML) - patients will be accepted in chronic phase or accelerated phase; patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy with PBSC autologous or conventional HSCT for advanced CML may be enrolled provided they are in CR or chronic phase (CP) and have < 5% marrow blasts at time of transplant
Myelodysplastic syndromes (MDS)/myeloproliferative disorder (MPD) - only patients with MDS/refractory anemia (RA) or MDS/refractory anemia with ringed sideroblasts (RARS) will be eligible for this protocol; additionally patients with myeloproliferative syndromes (MPS) will be eligible; those patients with MDS or MPS with > 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve < 5% marrow blasts at time of transplant
Renal cell carcinoma - must have evidence of disease not amenable to surgical cure or history of or active metastatic disease by radiological and histologic criteria

DONOR: FHCRC matching allowed will be grade 1.0 to 2.1; unrelated donors who are prospectively:

Matched for human leukocyte antigen (HLA)-A, B, C, DRB1 and DQB1 by high resolution typing
Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0201, and this type of mismatch is not allowed
DONOR: PBSC only will be permitted as a hematopoietic stem cell (HSC) source on this protocol

Exclusion Criteria:

Patients with rapidly progressive intermediate or high grade NHL

Renal cell carcinoma patients:

With expected survival of less than 6 months
Disease resulting in severely limited performance status (< 70%)
Any vertebral instability
History of brain metastases
Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
Females who are pregnant
Patients with non-hematological tumors except renal cell carcinoma
Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
Cardiac ejection fraction < 35%; ejection fraction is required if there is a history of anthracycline exposure or history of cardiac disease
Diffusion capacity of the lung for carbon monoxide (DLCO) < 40% and/or receiving supplementary continuous oxygen
The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules
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, 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
Karnofsky scores < 60 (except renal cell carcinoma [RCC])
Patients with > grade II hypertension by common toxicity criteria (CTC)
Human immunodeficiency virus (HIV) positive patients
The addition of cytotoxic agents for "cytoreduction" with the exception of hydroxyurea and imatinib mesylate will not be allowed within two weeks of the initiation of conditioning
DONOR: Marrow donors
DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for filgrastim (G-CSF) mobilization and harvest of PBSC

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

106

Study ID:

NCT00027820

Recruitment Status:

Completed

Sponsor:

Fred Hutchinson Cancer Center

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There are 10 Locations for this study

See Locations Near You

University of Arizona Health Sciences Center
Tucson Arizona, 85724, United States
Stanford University Hospitals and Clinics
Stanford California, 94305, United States
Emory University/Winship Cancer Institute
Atlanta Georgia, 30322, United States
OHSU Knight Cancer Institute
Portland Oregon, 97239, United States
Baylor Medical Center at Garland
Garland Texas, 75042, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City Utah, 84112, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle Washington, 98109, United States
Froedtert and the Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States
Universitaet Leipzig
Leipzig , D-041, Germany
University of Torino
Torino , 10126, Italy

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

106

Study ID:

NCT00027820

Recruitment Status:

Completed

Sponsor:


Fred Hutchinson Cancer Center

How clear is this clinincal trial information?

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