Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma
NCT ID: NCT00003196
Last Updated: 2019-12-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
63 participants
INTERVENTIONAL
1997-09-30
2002-04-30
Brief Summary
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Detailed Description
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I. To determine whether mixed hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen in patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma.
II. To determine whether mixed chimerism, established with non- myeloablative conditioning regimens, can be safely converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI).
OUTLINE:
CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive chemotherapy to reduce tumor size at discretion of primary physician and study investigators.
CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic peripheral blood stem cell (PBSC) transplant on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine intravenously (IV) twice daily (BID) on days -1 to 0 and then orally (PO) BID on days 1-35 with taper to day 56. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of graft-vs-host disease (GVHD) undergo DLI over 30 minutes on day 65 and may receive up to 3 additional infusions in the absence of GVHD and disease progression or persistence. Patients who have not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after a 2 month monitoring period.
After completion of study treatment, patients are followed up at 4, 6, 12, 18, and 24 months and then annually thereafter.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (irradiation, transplant, immunosuppression, DLI)
CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive chemotherapy to reduce tumor size at discretion of primary physician and study investigators.
CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic PBSC transplant on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 to 0 and then PO BID on days 1-35 with taper to day 56. Patients also receive mycophenolate mofetil PO BID on days 0-27.
POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of GVHD undergo DLI over 30 minutes on day 65 and may receive up to 3 additional infusions in the absence of GVHD and disease progression or persistence. Patients who have not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after a 2 month monitoring period.
chemotherapy
Undergo cytoreductive chemotherapy
total-body irradiation
Undergo TBI
peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplant
cyclosporine
Given IV or PO
mycophenolate mofetil
Given PO
allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplant
therapeutic allogeneic lymphocytes
Undergo DLI
Interventions
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chemotherapy
Undergo cytoreductive chemotherapy
total-body irradiation
Undergo TBI
peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplant
cyclosporine
Given IV or PO
mycophenolate mofetil
Given PO
allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplant
therapeutic allogeneic lymphocytes
Undergo DLI
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients \< 50 years of age with NHL, CLL and multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing chronic disease affecting kidneys, liver, lungs, and heart will be considered on a case by case basis and presented to professional clinical counselor (PCC)
* Patients \< 66 years of age with other 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; autografting must also be contraindicated in these patients and they must be approved for this protocol by both PCC and by the principal investigator; the following diseases are the likely candidates but other less common diseases may be considered and approved by PCC:
* Myelodysplastic syndromes
* Myeloproliferative syndromes
* Acute leukemia in remission
* Chronic myelogenous leukemia (CML) in 2nd chronic phase
* Hodgkin's disease
* Selected patients with any of the above diagnosis who are (a) older than 65 years and \< 75 years with a Karnofsky score \>= 70 and who, apart from age, fulfill eligibility criteria, or (b) \< 66 years but ineligible solely because of renal dysfunction; these patients must be approved for transplant by both PCC and the principal investigator
* DONOR: Human leukocyte antigen (HLA) genotypically identical sibling
* 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)
* DONOR: Age \< 75
Exclusion Criteria
* Patients with rapidly progressive high grade NHL
* History of 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 with a creatinine clearance \< 50 ml/min
* Cardiac ejection fraction \< 40% or cardiac failure requiring therapy
* 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
* DONOR: Identical twin
* DONOR: Age less than 12 years
* DONOR: Pregnancy
* DONOR: Infection with human immunodeficiency virus (HIV)
* DONOR: Inability to achieve adequate venous access
* DONOR: Known allergy to G-CSF
* DONOR: Current serious systemic illness
* DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for donation as described in the Standard Practice Guidelines
50 Years
65 Years
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
National Cancer Institute (NCI)
NIH
Fred Hutchinson Cancer Center
OTHER
Responsible Party
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Principal Investigators
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David Maloney
Role: PRINCIPAL_INVESTIGATOR
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Locations
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City of Hope Medical Center
Duarte, California, United States
Stanford University Hospitals and Clinics
Stanford, California, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Universitaet Leipzig
Leipzig, , Germany
University of Torino
Torino, , Italy
Countries
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References
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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.
Other Identifiers
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NCI-2012-00592
Identifier Type: REGISTRY
Identifier Source: secondary_id
#1225.00A
Identifier Type: -
Identifier Source: secondary_id
1225.00
Identifier Type: OTHER
Identifier Source: secondary_id
1225.00
Identifier Type: -
Identifier Source: org_study_id