Reduced-Intensity Conditioning Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma
Refractory Multiple Myeloma

About this trial
This is an interventional treatment trial for Refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria: Meet Salmon and Durie criteria for initial diagnosis of MM; transplant will be offered to patients with previously treated MM who meet one of the following criteria: Patient received at least one prior autologous or syngeneic hematopoietic SCT (HSCT) and now has progressive disease (PD) (greater than 25% increase in serum or urine paraprotein levels compared to best response status after autograft or appearance of new lytic bone lesions or plasmocytomas) Patient is not able to collect autologous PBSC due to poor marrow reserve (insufficient HSC-mobilization: < 2.5 x 10^6 cluster of differentiation [CD]34+ cells/kg); or contraindications to undergoing HSC-mobilization; patient now has PD and has received at least 4 cycles of standard chemotherapy (e.g. vincristine sulfate, doxorubicin hydrochloride, and dexamethasone [VAD]) in the past Patients must have the capacity to give informed consent DONOR: Human leukocyte antigen (HLA) genotypically identical sibling or phenotypically matched relative DONOR: HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria) Matched for serologically recognized HLA-A or B or C antigens and at least five of six HLA-A or B or C alleles Matched for HLA DRB1 and DQB1 alleles (defined by high-resolution typing) at the allele level DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis for PBSC collection DONOR: Donor must have adequate veins for leukapheresis or agree to placement of a temporary central venous catheter Exclusion Criteria: Karnofsky score < 60% Left ventricular ejection fraction < 40% or symptomatic heart failure; ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL,or symptomatic biliary disease Diffusion capacity of carbon monoxide (DLCO) < 50% (corrected) or receiving continuous supplemental oxygen Creatinine clearance < 40 mL/min Patients with poorly controlled hypertension Seropositive for the human immunodeficiency virus (HIV) Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence Pregnancy or breastfeeding Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment Not fully recovered from previous high-dose therapy: Persistent mucositis and gastrointestinal symptoms requiring hyperalimentation and/or intravenous hydration On steroids for autologous/syngeneic GVHD On IV antibiotics for documented infections Cytomegalovirus (CMV)-antigenemia positive On ganciclovir or foscarnet for previous CMV reactivation/infection; off of this therapy for less than two weeks despite documented CMV-antigenemia- negativity (identification [ID] should be consulted if there is persistent CMV antigenemia post autograft) Ongoing radiotherapy Patients who meet any of these criteria may be discussed with the principal investigator for recommendations as to the timing of the allograft Patients with active bacterial or fungal infections unresponsive to medical therapy DONOR: Identical twin DONOR: Donors unwilling to donate PBSC DONOR: Pregnancy DONOR: Infection with 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 stem cell donation DONOR: Age < 12 years DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
- University of Torino
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Related Donor
Unrelated Donor
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or TID on days 0-40 with taper to day 96 (unrelated donors).
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -3 and intermediate-dose melphalan IV over 15-20 minutes on day -2. Patients also undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 80 with taper to day 180 (related donors) or on days -3 to 100 with taper to day 180 (unrelated donors). Patients also receive mycophenolate mofetil PO BID on days 0-27 (related donors) or TID on days 0-40 with taper to day 96 (unrelated donors).