Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer
Induction of Mixed Hematopoietic Chimerism in Patients Using Fludarabine, Low Dose TBI, PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil
4 other identifiers
interventional
21
2 countries
2
Brief Summary
This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and donor stem cell transplant followed by cyclosporine, mycophenolate mofetil, and donor lymphocyte infusion in treating patients with hematopoietic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and total body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also keep the patient's immune response from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine 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 P25-P50 for phase_1
2 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
May 1, 2000
CompletedFirst Submitted
Initial submission to the registry
September 11, 2000
CompletedFirst Posted
Study publicly available on registry
June 9, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2005
CompletedJanuary 21, 2020
January 1, 2020
5.3 years
September 11, 2000
January 17, 2020
Conditions
Outcome Measures
Primary Outcomes (3)
Risk of graft rejection defined as the absence of detectable peripheral blood donor T cells with the addition of fludarabine phosphate
Up to day 56
Incidence of acute grade II/IV GVHD
Up to day 90 after the last DLI
Incidence of chronic GVHD
Up to 24 months
Secondary Outcomes (5)
Incidence of myelosuppression (ANC < 500/ul for > 2 days, platelets < 20,000/ul for > 2 days) after initial PBSC infusion
Up to day 56
Response of malignancy to DLI
Up to 24 months
Incidence of aplasia after DLI
Up to 24 months
Dose of CD3+ cells required to convert mixed to full lymphoid chimeras
Up to 24 months
Incidence of non-relapse mortality
Up to 24 months
Study Arms (1)
Treatment (fludarabine phosphate, TBI, PBSC transplant, DLI)
EXPERIMENTALCONDITIONING REGIMEN : Patients receive fludarabine phosphate IV on days - 4 to -2 and undergo low-dose TBI on day 0. (Note: Patients who have had an autologous transplant within 90 days prior to day 0 will not receive fludarabine phosphate.) PBSC INFUSION: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 35 with a taper to day 56. Patients receive mycophenolate mofetil PO BID on days 0-27. POST TRANSPLANT DLI: Patients with stable mixed chimerism on day 56, and without evidence of GVHD, undergo DLI IV over 30 minutes on day 65. Patients without a complete response, full donor chimerism, and GVHD after 2 months undergo further DLI at higher cell numbers. Up to 6 DLIs may be given 65 days apart.
Interventions
Undergo TBI
Given IV
Given PO
Given PO
Undergo allogeneic PBSC transplant
Undergo allogeneic PBSC transplant
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients aged \> 49 years and \< 75 years with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma who are not eligible for a curative autologous transplantation or who have failed prior autologous transplantation; patients with NHL and 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, 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
- Renal cell carcinoma
- Patients with other malignancies declining standard allografts may be approved for transplant following presentation and approval by the Fred Hutchinson Cancer Research Center (FHCRC) chimerism group
- DONOR:
- Human leukocyte antigen (HLA) genotypically or phenotypically identical related donor
- Donor must consent to granulocyte colony-stimulating factor (G-CSF) administration and leukopheresis
- Donor must have adequate veins for leukopheresis or agree to placement of central venous catheter (femoral, subclavian)
- Age \< 75 years
You may not qualify if:
- Eligible for a high-priority curative autologous transplant
- Patients with rapidly progressive aggressive NHL unless in minimal disease state
- Active 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%
- Severe defects in pulmonary function testing (defects are currently categorized as mild, moderate and severe) as defined by the pulmonary consultant, or receiving supplementary continuous oxygen
- Total bilirubin \> 2 x the upper limit of normal
- Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4 x the upper limit of normal
- Karnofsky score \< 50
- Patients with poorly controlled hypertension
- Patients with renal failure are eligible, however patients with renal compromise (serum creatinine greater than 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum cyclosporine levels
- DONOR:
- Identical twin
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
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)
Study Officials
- PRINCIPAL INVESTIGATOR
David Maloney
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
September 11, 2000
First Posted
June 9, 2004
Study Start
May 1, 2000
Primary Completion
September 1, 2005
Last Updated
January 21, 2020
Record last verified: 2020-01