Completed

Prolonged 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

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What is being tested

fludarabine phosphate

+ total-body irradiation
+ nonmyeloablative allogeneic hematopoietic stem cell transplantation
Drug
Radiation
Procedure
Other
Who is being recruted

Plasmablastic Lymphoma
+88

+ 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 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: September 1, 2003Actual 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 14, 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 enrolledTotal 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.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Plasmablastic Lymphoma
Lymphadenopathy
Urogenital Diseases
Adenocarcinoma
Anemia
Anemia, Refractory
Bacterial Infections and Mycoses
Blood Protein Disorders
Bone Marrow Diseases
Burkitt Lymphoma
Carcinoma
Carcinoma, Renal Cell
Cardiovascular Diseases
Chronic Disease
Disease
DNA Virus Infections
Female Urogenital Diseases and Pregnancy Complications
Hematologic Diseases
Hemorrhagic Disorders
Herpesviridae Infections
Hodgkin Disease
Immunoblastic Lymphadenopathy
Immune System Diseases
Immunoproliferative Disorders
Infections
Kidney Diseases
Kidney Neoplasms
Leukemia
Leukemia, Hairy Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Lymphatic Diseases
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Multiple Myeloma
Mycoses
Mycosis Fungoides
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Paraproteinemias
Pathologic Processes
Precancerous Conditions
Preleukemia
Recurrence
Sezary Syndrome
Syndrome
Tumor Virus Infections
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Vascular Diseases
Virus Diseases
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Acute
Lymphoma, B-Cell
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Hematologic Neoplasms
Epstein-Barr Virus Infections
Hemostatic Disorders
Lymphoma, Mantle-Cell
Disease Attributes
Female Urogenital Diseases
Male Urogenital Diseases
Leukemia, Large Granular Lymphocytic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms, Plasma Cell
Lymphoma, Extranodal NK-T-Cell
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic-Myeloproliferative Diseases
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.

Given IV

Undergo TBI

Undergo allogeneic PBMC transplantation

Undergo allogeneic PBMC transplantation

Given PO

Given PO or IV

Correlative studies
Study Objectives
Primary Objectives

Life-threatening GVHD defined as (1) death related to GVHD or its treatment, (2) disability caused by GVHD or its treatment (3) 3 or more major infections in a calendar year or (4) suicidal ideation because of GVHD.
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 ClinicsStanford, United StatesSee the location
Suspended
Rocky Mountain Cancer Centers-MidtownDenver, United States
Suspended
Emory University/Winship Cancer InstituteAtlanta, United States
Suspended
OHSU Knight Cancer InstitutePortland, United States
Completed10 Study Centers