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
Induction of Mixed Hematopoietic Chimerism in Older Patients With B-Cell Malignancies and in Selected Other Diseases, Using Low Dose TBI , PBSC Infusion and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil to be Followed by Donor Lymphocyte Infusion: A Pilot Study.
4 other identifiers
interventional
63
3 countries
5
Brief Summary
This pilot clinical trial studies low-dose total body irradiation and donor peripheral blood stem cell transplant followed by donor lymphocyte infusion in treatment patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma. Giving total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When 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. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Sep 1997
Longer than P75 for not_applicable
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
September 1, 1997
CompletedFirst Submitted
Initial submission to the registry
November 1, 1999
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2002
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2002
CompletedFirst Posted
Study publicly available on registry
July 19, 2004
CompletedDecember 27, 2019
December 1, 2019
4.6 years
November 1, 1999
December 24, 2019
Conditions
Outcome Measures
Primary Outcomes (5)
Incidence of GVHD, myelosuppression, and infections
At the conclusion of the study, all unexpected toxicities will be summarized and reported.
Up to 5 years
Greater than 10% incidence of treatment-related mortality (TRM) after PBSC infusion, defined as death without evidence of disease progression
Within 65 days of transplant
Greater than 20% incidence of TRM after DLI, defined as death without evidence of disease progression
Within 12 months of DLI
Proportion of patients who successfully achieve mixed chimerism
The proportion of patients who successfully establish mixed chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.
Up to 5 years
Proportion of patients with mixed chimerism who successfully achieve full donor chimerism
The proportion of patients with mixed chimerism who are successfully converted to full donor chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.
Up to 5 years
Secondary Outcomes (8)
Response of malignancy to DLI
Up to 5 years
Incidence of myelosuppression after initial PBSC transplant
Up to day 56
Incidence of aplasia after DLI
Up to day 90
Incidence of grades 2-4 acute GVHD after DLI
Up to day 90 post-DLI
Incidence of grades 2-4 acute GVHD after PBSC infusion
Up to day 56
- +3 more secondary outcomes
Study Arms (1)
Treatment (irradiation, transplant, immunosuppression, DLI)
EXPERIMENTALCYTOREDUCTION: 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.
Interventions
Undergo cytoreductive chemotherapy
Undergo TBI
Undergo allogeneic PBSC transplant
Given IV or PO
Given PO
Undergo allogeneic PBSC transplant
Undergo DLI
Eligibility Criteria
You may qualify if:
- Patients aged \> 49 years and \< 66 years with NHL, CLL and multiple myeloma who are not eligible for autologous transplantation or have failed prior autologous transplantation; patients with NHL and CLL must have failed prior therapy with an alkylating agent and/or fludarabine; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy
- 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
You may not qualify if:
- Eligible for autologous transplantation
- 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
- +5 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 (5)
City of Hope Medical Center
Duarte, California, 91010, United States
Stanford University Hospitals and Clinics
Stanford, California, 94305, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, 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
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 1, 1999
First Posted
July 19, 2004
Study Start
September 1, 1997
Primary Completion
April 1, 2002
Study Completion
April 1, 2002
Last Updated
December 27, 2019
Record last verified: 2019-12