Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
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
4 other identifiers
interventional
37
3 countries
10
Brief Summary
This phase I/II trial studies whether stopping cyclosporine before mycophenolate mofetil is better at reducing the risk of life-threatening graft-versus-host disease (GVHD) than the previous approach where mycophenolate mofetil was stopped before cyclosporine. The other reason this study is being done because at the present time there are no curative therapies known outside of stem cell transplantation for these types of cancer. Because of age or underlying health status, patients may have a higher likelihood of experiencing harm from a conventional blood stem cell transplant. This study tests whether this new blood stem cell transplant method can be made safer by changing the order and length of time that immune suppressing drugs are given after transplant.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2003
CompletedFirst Submitted
Initial submission to the registry
March 8, 2004
CompletedFirst Posted
Study publicly available on registry
March 9, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2006
CompletedJanuary 18, 2020
February 1, 2019
2.3 years
March 8, 2004
January 15, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of life-threatening GVHD in patients undergoing a modified taper of post-grafting immunosuppression after undergoing nonmyeloablative HSCT from matched unrelated donors
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.
1 year
Secondary Outcomes (4)
Need for corticosteroid treatment, defined as more than 1 mg/kg or equivalent of prednisone for more than 3 days at any time after transplant
1 year
Graft rejection
Up to day 365
Incidence of acute and chronic GVHD
Up to 7 years
Overall survival
Up to 7 years
Study Arms (1)
Treatment (prolonged MMF and truncated CSP)
EXPERIMENTALCONDITIONING: 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.
Interventions
Given IV
Undergo TBI
Undergo allogeneic PBMC transplantation
Undergo allogeneic PBMC transplantation
Given PO
Given PO or IV
Eligibility Criteria
You may qualify if:
- Ages \> 50 years with hematologic malignancies treatable by unrelated HCT
- 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:
- +4 more criteria
You may not qualify if:
- 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
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- National Cancer Institute (NCI)collaborator
Study Sites (10)
Stanford University Hospitals and Clinics
Stanford, California, 94305, United States
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado, 80218, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
OHSU Knight Cancer Institute
Portland, Oregon, 97239, 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 Memorial Lutheran Hospital, Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Universitaet Leipzig
Leipzig, D-04103, Germany
University of Tuebingen-Germany
Tübingen, D-72076, Germany
University of Torino
Torino, 10126, Italy
Related Publications (1)
Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
PMID: 32499241DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Brenda Sandmaier
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 8, 2004
First Posted
March 9, 2004
Study Start
September 1, 2003
Primary Completion
January 1, 2006
Last Updated
January 18, 2020
Record last verified: 2019-02