Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer
A Multi-Center Study of Nonmyeloablative Conditioning With TBI or Fludarabine/TBI for HLA-matched Related Hematopoietic Cell Transplantation for Treatment of Hematologic Malignancies With Post Grafting Immunosuppression With Tacrolimus and Mycophenolate Mofetil
4 other identifiers
interventional
150
2 countries
5
Brief Summary
This phase II trial studies how well tacrolimus and mycophenolate mofetil works in preventing graft-versus-host disease in patients who have undergone total-body irradiation (TBI) with or without fludarabine phosphate followed by donor peripheral blood stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI 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 tacrolimus and mycophenolate mofetil after the 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 Apr 2004
Longer than P75 for phase_2
5 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
April 1, 2004
CompletedFirst Submitted
Initial submission to the registry
August 4, 2004
CompletedFirst Posted
Study publicly available on registry
August 5, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2014
CompletedResults Posted
Study results publicly available
May 22, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2018
CompletedJanuary 29, 2020
December 1, 2019
9.9 years
August 4, 2004
April 14, 2017
January 17, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of Grade III/IV GVHD
Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL 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 with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades 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 with extreme constitutional symptoms or death
Day 180 post-transplantation
Incidence of Chronic Extensive GVHD
Number of patients who developed chronic extensive GVHD post-transplant. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
Day 180 post-transplantation
Secondary Outcomes (6)
Incidences of Graft Rejection
Day 180 post-transplantation
Overall Survival
At 1 year after conditioning
Incidences of Grades II-IV Acute GVHD
Day 180 post-transplantation
Rates of Disease Progression
Up to 5 years
Rates of Relapse-related Mortality
Up to 5 years
- +1 more secondary outcomes
Study Arms (2)
Arm I (nonmyeloablative conditioning with fludarabine and TBI)
EXPERIMENTALPatients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.
Arm II (nonmyeloablative conditioning with TBI)
EXPERIMENTALPatients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO.
Interventions
Given IV
Undergo radiotherapy
Given IV or PO
Given IV or PO
Undergo allogeneic peripheral blood stem cell transplant
Undergo allogeneic peripheral blood stem cell transplant
Correlative studies
Eligibility Criteria
You may qualify if:
- Patient must be not eligible for conventional allogeneic hematopoietic cell transplantation (HCT) and must have disease expected to be stable for at least 100 days without chemotherapy; patients with hematologic malignancies treatable with HCT or with a B cell malignancy except those curable with autologous transplant will be included; patients not eligible for active disease specific protocols may be enrolled in this protocol; patients will include the following
- Diffuse large B cell non-Hodgkin lymphoma (NHL) and other aggressive lymphomas - not eligible for conventional myeloablative HCT or after autologous HCT
- Low grade NHL- with \< 6 months duration of complete response (CR) between courses of conventional therapy
- Mantle cell NHL- may be treated in first CR
- Chronic lymphocytic leukemia (CLL) - must have either 1) 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. 2-chlorodeoxyadenosine \[2-CDA\], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); 2) failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; or 3) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or a diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL
- Hodgkin lymphoma (HL) - must have received and failed frontline therapy; patients must have failed or were not eligible for autologous transplant
- Multiple myeloma (MM) - following a planned autologous transplant or equivalent high-dose therapy without a graft, or following a failed prior autograft
- Acute myeloid leukemia (AML) - must have \< 5% marrow blasts at the time of transplant
- Acute lymphoblastic leukemia (ALL) - must have \< 5% marrow blasts at the time of transplant
- Chronic myelogenous leukemia (CML) - patients will be accepted beyond first chronic phase (CP1) if they have received previous myelosuppressive chemotherapy or HCT, and have \< 5% marrow blasts at time of transplant
- Myelodysplastic syndromes/myeloproliferative disorders (MDS/MPD) - must have received previous myelosuppressive chemotherapy or HCT, and have \< 5% marrow blasts at time of transplant
- Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy
- Myelosuppressive chemotherapy must be discontinued three weeks prior to conditioning with the exception of hydroxyurea or imatinib
- Patients \< 12 years old must be approved by both the participating institutions' patient review committee such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and the FHCRC principal investigator
- Patients with human leukocyte antigen (HLA)-matched related donors
- +4 more criteria
You may not qualify if:
- Eligible for a high priority curative autologous transplant
- Patient with rapidly progressive, aggressive NHL unless in minimal disease state
- Patients with chronic myelomonocytic leukemia (CMML)
- Life expectancy severely limited by diseases other than malignancy
- Any current 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, ALL or CML
- Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment
- Female patients who are pregnant or breastfeeding
- Human immunodeficiency virus (HIV)-positive patients
- Fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month
- Karnofsky score \< 50 for adult patients
- Lansky-Play performance score \< 50 for pediatric patients
- Symptomatic coronary artery disease or ejection fraction \< 35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of \< 26%); ejection fraction is required if age \> 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction \< 26% may be enrolled if approved by a cardiologist
- Poorly controlled hypertension
- Diffusing capacity of the lung for carbon monoxide (DLCO) \< 30%, total lung capacity (TLC) \< 30%, forced expiratory volume in one second (FEV1) \< 30% and/or receiving supplementary continuous oxygen; the FHCRC principal investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (5)
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
LDS Hospital
Salt Lake City, Utah, 84143, United States
VA Puget Sound Health Care System
Seattle, Washington, 98101, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
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)
Results Point of Contact
- Title
- David G Maloney, MD PhD
- Organization
- Fred Hutch
Study Officials
- PRINCIPAL INVESTIGATOR
David Maloney
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
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 4, 2004
First Posted
August 5, 2004
Study Start
April 1, 2004
Primary Completion
March 1, 2014
Study Completion
July 1, 2018
Last Updated
January 29, 2020
Results First Posted
May 22, 2017
Record last verified: 2019-12