Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies
Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression
3 other identifiers
interventional
160
3 countries
11
Brief Summary
This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with fludarabine phosphate, cyclosporine, and mycophenolate mofetil before 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 not_applicable
11 active sites
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Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2000
CompletedFirst Submitted
Initial submission to the registry
April 10, 2001
CompletedFirst Posted
Study publicly available on registry
January 27, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2005
CompletedJanuary 21, 2020
January 1, 2020
4.2 years
April 10, 2001
January 17, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
Probability of severe (grade III/IV) GVHD in each arm
95% confidence interval will be calculated.
Up to day 84
Probability of severe (grade III/IV) GVHD in each arm
95% confidence intervals will be calculated.
Up to 5 years
Secondary Outcomes (8)
Incidence of graft rejection
Day 28
Incidence of graft rejection
Day 56
Incidence of graft rejection
Day 84
Incidence of graft rejection
Day 180
Incidence of graft rejection
Day 365
- +3 more secondary outcomes
Study Arms (2)
Arm I (indolent disease)
EXPERIMENTALCONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.
Arm II (aggressive disease)
EXPERIMENTALCONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.
Interventions
Given IV
Undergo TBI
Undergo PBSCT
Undergo PBSCT
Given PO or IV
Given IV or PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or multiple myeloma who are not eligible for a curative autologous transplantation or who have received a prior autologous transplantation; patients with NHL or CLL must have failed prior therapy with an alkylating agent and/or fludarabine, or be at high risk of relapse; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy
- Patients \< 50 years of age with NHL, Hodgkin's disease (HD), CLL or multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing medical conditions
- Patients \< 75 years of age with other malignant diseases treatable by allogeneic bone marrow transplant (BMT) whom through pre-existing chronic disease affecting kidneys, liver, lungs, and heart are considered to be at high risk for regimen related toxicity using standard high dose regimens; the following diseases are the likely candidates
- Myelodysplastic syndromes
- Myeloproliferative syndromes
- Acute Leukemia with \< 10% blasts
- Amyloidosis
- Hodgkin's disease
- The Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) may approve patients with other malignancies or patients declining standard allografts for transplant following presentation and approval; centers outside the FHCRC that have a PCC or equivalent should obtain their Institutional approval; if there is not a comparable group at the Institution, please contact the FHCRC Principal Investigator for FHCRC approval through PCC
- DONOR: Human leukocyte antigen (HLA) genotypically or phenotypically identical related donor
- DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
You may not qualify if:
- Eligible for a high-priority curative autologous transplant
- Patients with rapidly progressive aggressive NHL unless in minimal disease state
- Any current central nervous system (CNS) involvement with disease
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Females who are pregnant
- Patients who are human immunodeficiency virus (HIV) positive
- Cardiac ejection fraction \< 40%; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
- Receiving supplementary continuous oxygen
- Diffusing capacity of the lung for carbon monoxide (DLCO) \< 30%
- Total lung capacity (TLC) \< 30%
- Forced expiratory volume in one second (FEV1) \< 30%
- Total bilirubin \> 2x the upper limit of normal
- Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4x the upper limit of normal
- Karnofsky score \< 50
- Patients with poorly controlled hypertension who are unable to have blood pressure kept below 150/90 on standard medication
- +9 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 (11)
University of Arizona Health Sciences Center
Tucson, Arizona, 85724, United States
City of Hope Medical Center
Duarte, California, 91010, United States
Stanford University Hospitals and Clinics
Stanford, California, 94305, United States
OHSU Knight Cancer Institute
Portland, Oregon, 97239, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
LDS Hospital
Salt Lake City, Utah, 84143, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Froedtert Hospital
Milwaukee, Wisconsin, 53226-3596, United States
Universitaet Leipzig
Leipzig, D-04103, 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
David Maloney
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 10, 2001
First Posted
January 27, 2003
Study Start
December 1, 2000
Primary Completion
February 1, 2005
Last Updated
January 21, 2020
Record last verified: 2020-01