|No phase specified||Treatment||Closed||50 to 75||NCI, Other||1225.00|
NCI-2012-00592, FHCRC-1225.00, NCI-G98-1374, NCT00003196
It is known that immune reactions of the donor cells against cancer contribute significantly to the ability to achieve cure after bone marrow transplant (BMT). This research study will test an approach to treating cancer that uses immune cells from the donor to fight the cancer cells. The main reason for using this treatment is the evidence that strong immune responses can occur from donor cells and remissions from cancer have been reported in patients whose cancer came back after a bone marrow transplant. This type of treatment is called a donor leukocyte infusion or DLI. It has been shown that it is possible to get complete remissions of the cancer by using DLI. Most success with the use of DLI has been in a form of leukemia called chronic myeloid leukemia. However, there is good evidence that this effect can occur in other diseases including multiple myeloma, lymphoma, and chronic lymphocytic leukemia. This type of immune response against cancer cells is usually called a graft-versus-leukemia (GVL) effect
Further Study Information
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).
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.
- 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 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 principle 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
- 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 glutamic 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
Trial Lead Organizations/Sponsors
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumNational Cancer Institute
National Heart, Lung, and Blood Institute
|David G. Maloney||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00003196
ClinicalTrials.gov processed this data on September 30, 2013
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