Completed

Reduced Life-Threatening GVHD Through Prolonged Mycophenolate Mofetil and Truncated Cyclosporine After Unrelated Donor Transplant for Hematologic Malignancies and Renal Cell Carcinoma

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What is being tested

fludarabine phosphate

+ total-body irradiation

+ nonmyeloablative allogeneic hematopoietic stem cell transplantation

DrugRadiationProcedureOther
Who is being recruted

Congenital Abnormalities+85

+ Lymphadenopathy

+ Urogenital Diseases

See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1 & 2
Interventional
Study Start: September 2003
See protocol details

Summary

Principal SponsorFred Hutchinson Cancer Center
Last updated: January 28, 2026
Sourced from a government-validated database.Claim as a partner

Study start date: September 1, 2003

Actual date on which the first participant was enrolled.

PRIMARY OBJECTIVES: I. To determine whether the incidence of life-threatening GVHD can be reduced after unrelated donor peripheral blood mononuclear cell (PBMC) hematopoietic cell transplantation (HCT) using nonmyeloablative conditioning with earlier discontinuation of cyclosporine (CSP) and extended administration of mycophenolate mofetil (MMF) in patients with hematologic malignancies and metastatic renal cell carcinoma. SECONDARY OBJECTIVES: I. To compare the incidence of acute and chronic GVHD to protocols 1463 and 1641. II. To compare the utilization of corticosteroids to protocols 1463 and 1641. III. To compare survival to that achieved under protocol 1463 and 1641. OUTLINE: CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2, and undergo total-body irradiation (TBI) on day 0. TRANSPLANTATION: Patients undergo allogeneic PBMC transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 80 with taper to day 150 and mycophenolate mofetil PO or IV thrice daily (TID) on days 0-30, BID on days 31-150, and then taper to day 180. Treatment continues in the absence of unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 24 months and then yearly for 5 years.

Official TitleProlonged Mycophenolate Mofetil and Truncated Cyclosporine Postgrafting Immunosuppression to Reduce Life-Threatening GVHD After Unrelated Donor Peripheral Blood Cell Transplantation Using Nonmyeloablative Conditioning for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-Center Trial
NCT00078858
Principal SponsorFred Hutchinson Cancer Center
Last updated: January 28, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

37 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.



Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Congenital AbnormalitiesLymphadenopathyUrogenital DiseasesAdenocarcinomaAnemiaAnemia, RefractoryBlood Protein DisordersBone Marrow DiseasesBurkitt LymphomaCarcinomaCarcinoma, Renal CellCardiovascular DiseasesChronic DiseaseDNA Virus InfectionsFemale Urogenital Diseases and Pregnancy ComplicationsHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersHerpesviridae InfectionsHodgkin DiseaseImmunoblastic LymphadenopathyImmune System DiseasesImmunoproliferative DisordersInfectionsKidney DiseasesKidney NeoplasmsLeukemiaLeukemia, Hairy CellLeukemia, LymphoidLeukemia, MyeloidLymphatic DiseasesLymphomaLymphoma, FollicularLymphoma, Non-HodgkinLymphoproliferative DisordersWaldenstrom MacroglobulinemiaMultiple MyelomaMycosis FungoidesMyelodysplastic SyndromesMyeloproliferative DisordersCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesNeoplasmsNeoplasms by Histologic TypeNeoplasms by SiteNeoplasms, Glandular and EpithelialParaproteinemiasPathologic ProcessesRecurrenceSezary SyndromePathological Conditions, Signs and SymptomsTumor Virus InfectionsUrogenital NeoplasmsUrologic DiseasesUrologic NeoplasmsVascular DiseasesVirus DiseasesLeukemia, B-CellLeukemia, Lymphocytic, Chronic, B-CellLeukemia, T-CellLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, Myeloid, Accelerated PhaseLeukemia, Myeloid, Chronic-PhaseLeukemia, Myeloid, AcuteLeukemia, Myelomonocytic, ChronicHistiocytosisHistiocytic Disorders, MalignantLymphoma, B-CellLymphoma, T-CellLymphoma, Large-Cell, ImmunoblasticLymphoma, Large B-Cell, DiffuseLymphoma, T-Cell, CutaneousLymphoma, T-Cell, PeripheralLymphoma, Large-Cell, AnaplasticLymphoma, B-Cell, Marginal ZoneEpstein-Barr Virus InfectionsHemostatic DisordersLymphoma, Mantle-CellDisease AttributesFemale Urogenital DiseasesMale Urogenital DiseasesLeukemia, Large Granular LymphocyticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaNeoplasms, Plasma CellLymphoma, Extranodal NK-T-CellLeukemia, Myelomonocytic, JuvenileMyelodysplastic-Myeloproliferative DiseasesDendritic Cell Sarcoma, Interdigitating

Criteria

Inclusion Criteria: * Ages \> 50 years with hematologic malignancies treatable by unrelated HCT * Ages =\< 50 years of age with hematologic diseases treatable by allogeneic HCT 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 HCT; 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 high-dose transplantation do not require patient review committee approval; all children \< 12 years must be discussed with the FHCRC primary 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: * Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B cell NHL-not eligible for autologous hematopoietic stem cell transplant (HSCT), not eligible for conventional myeloablative HSCT, or after failed autologous HSCT * Low grade NHL- with \< 6 month duration of complete remission (CR) between courses of conventional therapy * Mantle cell NHL-may be treated in first CR * Chronic lymphocytic leukemia (CLL)- Must be refractory to fludarabine; patients who fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-cladribine \[CDA\], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog) * Hodgkin 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 HCT is permitted * Acute myeloid leukemia (AML)- must have \< 5% marrow blasts at the time of transplant. * Acute lymphocytic leukemia (ALL)- must have \< 5% marrow 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 filgrastim (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMC) autologous or conventional HCT for advanced CML may be enrolled provided they are in CR or CP and have \< 5% marrow blasts at time of transplant * Myelodysplastic syndrome (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, major histocompatibility complex, class II, DR beta 1 (DRB1) and major histocompatibility complex, class II, DQ beta 1 (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 in the graft rejection vector 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: G-PBMC only will be permitted as a 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 * Diffusing 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, bridging fibrosis, 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 G-CSF mobilization and harvest of G-PBMC

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

One single intervention group is designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

Experimental
CONDITIONING: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, and undergo TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBMC transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 150 and mycophenolate mofetil PO or IV TID on days 0-30, BID on days 31-150, and then taper to day 180. Treatment continues in the absence of unacceptable toxicity.

Study 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 10 locations

Suspended

Stanford University Hospitals and Clinics

Stanford, United StatesOpen Stanford University Hospitals and Clinics in Google Maps
Suspended

Rocky Mountain Cancer Centers-Midtown

Denver, United States
Suspended

Emory University/Winship Cancer Institute

Atlanta, United States
Suspended

OHSU Knight Cancer Institute

Portland, United States
Completed10 Study Centers