Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
A Randomized Phase II Study to Determine the Most Promising Postgrafting Immunosuppression for Prevention of Acute GVHD After Unrelated Donor G-CSF Mobilized Peripheral Blood Mononuclear Cell (G-PBMC) Transplantation Using Nonmyeloablative Conditioning for Patients With Hematologic Malignancies A Multi-Center Trial
4 other identifiers
interventional
210
3 countries
11
Brief Summary
This randomized phase II trial studies how well giving tacrolimus and mycophenolate mofetil (MMF) with or without sirolimus works in preventing acute graft-versus-host disease (GVHD) in patients undergoing donor stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body-irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving MMF and tacrolimus with or without sirolimus after transplant may stop this from happening.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2004
Longer than P75 for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2004
CompletedFirst Submitted
Initial submission to the registry
March 3, 2005
CompletedFirst Posted
Study publicly available on registry
March 4, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
May 8, 2015
CompletedResults Posted
Study results publicly available
September 15, 2015
CompletedOctober 30, 2019
October 1, 2019
6.5 years
March 3, 2005
August 13, 2015
October 29, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants With Grades II-IV Acute GVHD
Number of patients with grades II-IV acute GVHD aGVHD Stages Skin: 1. a maculopapular eruption involving \< 25% BSA 2. a maculopapular eruption involving 25 - 50% BSA 3. generalized erythroderma 4. generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. bilirubin 2.0 - 3.0 mg/100 mL 2. bilirubin 3 - 5.9 mg/100 mL 3. bilirubin 6 - 14.9 mg/100 mL 4. bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients w/ visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
150 days after transplant
Secondary Outcomes (4)
Number of Non-Relapse Mortalities
200 days after transplant
Number of Participants Utilizing High-Dose Corticosteroids
150 days after transplant
Number of Participants Surviving Overall
1 Year post-transplant
Number of Participants Surviving Without Progression
2 Years post-transplant
Study Arms (3)
Arm I (MMF and tacrolimus)
ACTIVE COMPARATORPatients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.
Arm II (MMF and tacrolimus alternate schedule)
EXPERIMENTALPatients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.
Arm III (MMF, tacrolimus, and sirolimus)
EXPERIMENTALPatients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.
Interventions
Given IV
Undergo total-body irradiation
Undergo allogeneic peripheral blood stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplantation
Given IV or PO
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Ages \> 50 years with hematologic malignancies treatable by unrelated hematopoietic cell transplant (HCT)
- Patients =\< 50 years of age who have received previous high-dose transplantation do not require patient review committee approvals (All children \< 12 years must be discussed with the FHCRC principal investigator (PI) \[Brenda Sandmaier, MD 206 6674961\] prior to registration)
- Ages =\< 50 years of age with chronic lymphocytic leukemia (CLL); these patients do not require patient review committee approvals
- The following diseases will be permitted although other diagnoses can be considered if approved by PCC or the participating institutions' patient review committees and the principal investigators:
- Aggressive non-Hodgkin lymphomas (NHL) 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
- Mantle Cell NHL may be treated in first complete response (CR) (Diagnostic lumbar puncture \[LP\] required pretransplant)
- Low grade NHL with \< 6 month duration of CR between courses of conventional therapy
- CLL must have either
- Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine phosphate (FLU) (or another nucleoside analog, e.g. Cladribine \[2-CDA\], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog);
- Failed FLU-CY-Rituximab (FCR) combination chemotherapy at any time point; or
- Have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR
- Hodgkin Lymphoma must have received and failed frontline therapy
- Multiple Myeloma 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
- +8 more criteria
You may not qualify if:
- Patients with rapidly progressive intermediate or high grade NHL
- Patients with a diagnosis of chronic myelomonocytic leukemia (CMML)
- Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
- Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, MDS, ALL or CML
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Females who are pregnant or breast-feeding
- Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years
- 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 age \> 50 years or there is a history of anthracycline exposure or history of cardiac disease
- Diffusion capacity of carbon monoxide (DLCO) \< 40%, total lung capacity (TLC) \< 40%, forced expiratory volume in one second (FEV1) \< 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, or symptomatic biliary disease
- Karnofsky score \< 60 or Lansky score \< 50
- Patient has poorly controlled hypertension and on multiple antihypertensives
- Human immunodeficiency virus (HIV) positive patients
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (11)
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
LDS Hospital
Salt Lake City, Utah, 84143, United States
Veterans Administration Center-Seattle
Seattle, Washington, 98108, 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
Rigshospitalet University Hospital
Copenhagen, 2100, Denmark
Medizinische Univ Klinik Koln
Cologne, 50924, Germany
Universitaet Leipzig
Leipzig, D-04103, Germany
University of Tuebingen-Germany
Tübingen, D-72076, Germany
Related Publications (2)
Kornblit B, Maloney DG, Storer BE, Maris MB, Vindelov L, Hari P, Langston AA, Pulsipher MA, Bethge WA, Chauncey TR, Lange T, Petersen FB, Hubel K, Woolfrey AE, Flowers ME, Storb R, Sandmaier BM. A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation. Haematologica. 2014 Oct;99(10):1624-31. doi: 10.3324/haematol.2014.108340. Epub 2014 Aug 1.
PMID: 25085357RESULTCooper 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)
Results Point of Contact
- Title
- Dr. Brenda M. Sandmaier
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Brenda Sandmaier
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 3, 2005
First Posted
March 4, 2005
Study Start
November 1, 2004
Primary Completion
May 1, 2011
Study Completion
May 8, 2015
Last Updated
October 30, 2019
Results First Posted
September 15, 2015
Record last verified: 2019-10