Study to test feasibility and efficacy of T-replete Bone Marrow (BM), infused after a RIC regimen and post-transplantation Cyclophosphamide (Cy), in patients with poor prognosis lymphomas.
Allogeneic stem cell transplantation (ALLO) is the treatment of choice for many hematological diseases. However, HLA identical donor (sibling or unrelated) is available for 50-60% of patients and alternative donors are needed. Haploidentical donors have been used for many years, mostly after extensive T-cell depletion of peripheral stem cell, to avoid Graft Versus Host Disease (GVHD). Recently, promising data have been reported with haploidentical transplantation using T-replete bone marrow (BM) and high-dose cyclophosphamide (Cy) post-transplantation. However, the conditioning regimen did not contain drugs active against hemopathies, enhancing the relapse risk. In this study, the investigators want to test the feasibility and efficacy of T-replete BM, infused after a RIC regimen and post-transplantation Cy, in patients with poor prognosis lymphoproliferative diseases. The RIC regimen consisted of modified regimen used in different studies conducted in Italy on behalf GITMO.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Thiotepa (10 mg/kg /day) will be administered every 12 h, at day -6
Fludarabine (30mg/m2/day x 4 days) will be dosed according to renal function. For decreased creatinine clearance (CCr) (≤ 61 mL/min) Fludarabine dosage should be reduced as follows: CCr 46-60 mL/min, fludarabine = 24 mg/ m2/day
Pre-transplantation Cyclophosphamide(Cy) 30 mg/kg/day will be administered as a 1-2 hour intravenous infusion with a high volume fluid flush on Days -5. Cy will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the Adjusted IBW (AIBW) Cyclophosphamide \[50 mg/kg/day IBW\] will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).
Istituto Clinico Humanitas
Rozzano, MI, Italy
RECRUITINGProcedure activity
1-year Progression Free Survival (PFS) to evaluate the activity of the procedure (taking into account an excess of toxicity). It is assumed that at 1-year a proportion of patients progression free of 20% or lower will be considered to be clinically unworthy, whereas a proportion of 40% or higher will be assumed to be of potential interest.
Time frame: 1 year
Neutrophils recovery
Neutrophils will be measured at different time points of increasing lenght up to 1 year after transplant and then if clinically indicated
Time frame: 1 year
Platelets recovery
Platelets will be measured at different time points of increasing lenght up to 1 year after transplant and then if clinically indicated
Time frame: 1 year
Incidence of graft failure
Time frame: 1 year
Cumulative incidence of acute and chronic GVHD
Time frame: 1 year
Incidence of infections
Possible infections will be monitored for a time period of 1 year post-transplantation and then if clinically required
Time frame: 1 year
Cumulative incidence of relapse/progression
Time frame: 1 year
Treatment related mortality (TRM)
Time frame: 1 year
Immunological reconstitution
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T, B and NK subsets will be analysed in deep using cytofluorimetry and functional tests.
Time frame: 1 year