Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer
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Purpose
The reason for doing this study is to determine 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
| Condition | Intervention | Phase |
|---|---|---|
|
Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission 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 Grade III Lymphomatoid Granulomatosis 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 Grade III Lymphomatoid Granulomatosis Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Childhood Renal Cell Carcinoma Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia Clear Cell Renal Cell Carcinoma Contiguous Stage II Adult Burkitt Lymphoma Contiguous Stage II Adult Diffuse Large Cell Lymphoma Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma Contiguous Stage II Adult Lymphoblastic Lymphoma Contiguous Stage II Grade 3 Follicular Lymphoma Contiguous Stage II Mantle Cell Lymphoma de Novo Myelodysplastic Syndromes Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Juvenile Myelomonocytic Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Burkitt Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder 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 Anemia Refractory Anemia With Ringed Sideroblasts Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Splenic Marginal Zone Lymphoma Stage I Adult Burkitt Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Mixed Cell Lymphoma Stage I Adult Immunoblastic Large Cell Lymphoma Stage I Adult Lymphoblastic Lymphoma Stage I Adult T-cell Leukemia/Lymphoma Stage I Childhood Anaplastic Large Cell Lymphoma Stage I Childhood Large Cell Lymphoma Stage I Childhood Lymphoblastic Lymphoma Stage I Childhood Small Noncleaved Cell Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage II Adult T-cell Leukemia/Lymphoma Stage II Childhood Anaplastic Large Cell Lymphoma Stage II Childhood Large Cell Lymphoma Stage II Childhood Lymphoblastic Lymphoma Stage II Childhood Small Noncleaved Cell Lymphoma Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Adult T-cell Leukemia/Lymphoma Stage III Childhood Anaplastic Large Cell Lymphoma Stage III Childhood Large Cell Lymphoma Stage III Childhood Lymphoblastic Lymphoma Stage III Childhood Small Noncleaved Cell Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Childhood Anaplastic Large Cell Lymphoma Stage IV Childhood Large Cell Lymphoma Stage IV Childhood Lymphoblastic Lymphoma Stage IV Childhood Small Noncleaved Cell Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Renal Cell Cancer T-cell Large Granular Lymphocyte Leukemia Type 1 Papillary Renal Cell Carcinoma Type 2 Papillary Renal Cell Carcinoma Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Childhood Acute Lymphoblastic Leukemia Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies Waldenström Macroglobulinemia |
Drug: fludarabine phosphate Radiation: total-body irradiation Procedure: peripheral blood stem cell transplantation Drug: cyclosporine Drug: mycophenolate mofetil Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Low-Dose TBI and Fludarabine Followed by Nonmyeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation Using Enhanced Postgrafting Immunosuppression for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-Center Trial. |
- Risk of true graft rejection in patients with and without preceding chemotherapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The goal is to reduce the risk in patients without preceding chemotherapy to < 20% and with preceding chemotherapy to < 10%.
- Risk of grades II-IV acute GVHD in those patients with sustained engraftment [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]We hope to reduce the incidence of grades II-IV acute GVHD from 50% to less than 35% in patients with sustained engraftment by increasing the dosing of MMF to q 8 hrs. We will describe the impact of the enhanced post-grafting immunosuppression on objective measures of GVHD. These include doses and duration of immunosuppression (in particular corticosteroids) and number of GVHD treatment regimens used within the first year. These parameters will be compared to the results of protocol 1463.
- Incidence of reversing impending graft rejection (less than 40% donor CD3+ T cell chimerism) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 150 |
| Study Start Date: | August 2001 |
| Primary Completion Date: | September 2004 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (PBSCT)
REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV on days -4, -3, and -2 and undergo TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO 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. |
Drug: fludarabine phosphate
Given IV
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: peripheral blood stem cell transplantation
Undergo nonmyeloablative PBSCT
Other Names:
Drug: cyclosporine
Given PO
Other Names:
Drug: mycophenolate mofetil
Given PO
Other Names:
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative PBSCT
|
Detailed 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.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation (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.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Arizona | |
| University of Arizona Health Sciences Center | |
| Tucson, Arizona, United States, 85724 | |
| United States, California | |
| Stanford University | |
| Stanford, California, United States, 94305 | |
| United States, Georgia | |
| Emory University | |
| Atlanta, Georgia, United States, 30322 | |
| United States, Oregon | |
| OHSU Knight Cancer Institute | |
| Portland, Oregon, United States, 97239 | |
| United States, Texas | |
| Baylor Medical Center | |
| Garland, Texas, United States, 75042 | |
| United States, Utah | |
| University of Utah | |
| Salt Lake City, Utah, United States, 84057 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| United States, Wisconsin | |
| Froedtert Memorial Lutheran Hospital, Medical College of Wisconsin | |
| Milwaukee, Wisconsin, United States, 53226 | |
| Germany | |
| Universitaet Leipzig | |
| Leipzig, Germany, D-04103 | |
| Italy | |
| University of Torino | |
| Torino, Italy, 10126 | |
| Principal Investigator: | Brenda Sandmaier | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
No publications provided
| Responsible Party: | Sandmaier, Brenda, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00027820 History of Changes |
| Other Study ID Numbers: | 1641.00, NCI-2012-00591, P01CA018029, P01HL036444 |
| Study First Received: | December 7, 2001 |
| Last Updated: | April 19, 2013 |
| Health Authority: | United States: Federal Government |
Additional relevant MeSH terms:
|
Congenital Abnormalities Anemia Anemia, Refractory Burkitt Lymphoma Neoplasms Carcinoma Carcinoma, Renal Cell Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Hairy Cell Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute |
Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis Lymphoproliferative Disorders Waldenstrom Macroglobulinemia Multiple Myeloma Neoplasms, Plasma Cell |
ClinicalTrials.gov processed this record on May 16, 2013