Pediatric and adult patients (aged from 1 to 70 years) with hematologic malignancies (leukemia, myeloma, lymphoma), candidates for allogeneic transplantation from HLA-identical or HLA-mismatched family is from the register. MedDRA version: 14.1 Level: PT Classification code 10001756 Term: Allogenic bone marrow transplantation therapy System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: FLUDARA*EV 5FL 50MG
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: fludarabina
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg/ml mil
Sponsors
FONDAZIONE CENTRO S. RAFFAELE DEL MONTE TABOR
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with hematological malignancies such as - acute myeloid leukaemia -AML- in CR1 except “low-risk cases” defined by: t(15;17); t(8;21); inv 16; normal cytogenetics at diagnosis with FLT3-ITD negative and NPM-1 positive (with any high-risk clinical criteria). - any AML beyond CR1 - acute lymphoblast leukaemia -ALL- in CR1 only if at “high risk” defined by cytogenetics as t(9;22), t(4;11), or for persistence of minimal residual disease (MRD) after consolidation. - any ALL beyond CR1 - chronic myeloid leukaemia -CML- in chronic phase (CP) or accelerated phase (AP) intolerant/not responsive to TKinhibitors, in blastic phase (BP) - myeloproliferative neoplasia –MPD- - myelodysplastic syndrome -MDS- with intermediate or high risk International Prognostic Scoring System (IPSS) - diffuse large cell lymphoma –DLCL- with a chemosensitive relapse or beyond CR1 - lymphoblastic and Burkitt lymphoma with a chemosensitive relapse or beyond CR1 - mantle cell lymphoma –MCL- with a chemosensitive relapse or beyond CR1 - follicular lymphoma –FCL- with a chemosensitive relapse or beyond CR2 - Hodgkin lymphoma -HD- with a chemosensitive relapse or beyond CR1 - chronic lymphocytic leukaemia –CLL- at “poor risk” in CR1 or with a chemosensitive relapse - T-cell non Hodgkin lymphoma –T-NHL- in CR1 or beyond - multiple myeloma –MM- at high risk for cytogenetics or ISS stage 3 in CR1 following high dose chemotherapy - MM at any relapse/progression, except refractory disease · ECOG > 2 · Age 3x10e7/kg* 5/6 TNC > 4x10e7/kg* 4/6 TNC > 5x10e7/kg* · If a single CBU doesn’t reach the target dose, then two CBUs are preferred. * This values are intented at the moment of collection. Are the trial subjects under 18? yes Number of subjects for this age range: 34 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. A hematopoietic cell transplantation-specific comorbidity index (Sorror et al Appendix B) > 4 2. Active non-controlled infectious disease at the moment of inclusion 3. Active HBV or HCV infection 4. Impaired liver function (Bilirubin > 2.0 x upper normal limit; Transaminases > 3.0 x upper normal limit) 5. Impaired renal function (Creatinine-clearance 1.5 x upper normal limit). 6. Pleural effusion or ascites > 1.0 L 7. Pregnancy or lactation 8. Known hypersensitivity to treosulfan and/or fludarabine and/or rapamycin 9. Non-co-operative behaviour or non-compliance 10. Psychiatric diseases or conditions that might impair the ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of progression free survival (PFS) at 365 days;Secondary Objective: Efficacy - Evaluation of engraftment - Evaluation of relapse incidence (RI) - Documentation of donor chimerism on day +28 and +100 Safety - Evaluation of incidence of non-relapse mortality (NRM) on day +28, day +100 and +360 - Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD). - EBV reactivation End of total follow up for OS, PFS, RI, NRM, cGvHD = 365 days after transplantation of the last patient included;Primary end point(s): Progression-free survival (PFS) within 1 year after transplantation is measured from time of start of HSCT (= day -7) to time of progression event. Progression events are defined as relapse of disease in patients in CR at the moment of transplant and progressive desease in the others. Relapse is defined according to “WHO diagnostic criteria”. Progressive diseases is defined as increasing of 25% of the bulk of disease parameters (blast for leukemia, lymphonodes diameters for lymphoma, monoclonal paraprotein in MM).;Timepoint(s) of evaluation of this end point: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy - Engraftment Is defined as neutrophil = 500*109/L, Hemoglobin = 8 gr/L, Platelets = 20000*10^9/L without transfusion or growth factor administration for consecutively three days. - Relapse incidence (RI) Is defined as reappearance of disease according to “WHO diagnostic criteria” until at the end of total follow-up. - Donor chimerism course = 95% on day +28, +100 Safety - Non-relapse mortality (NRM) until 365 days after transplant - Acute graft vs. host disease (aGvHD) until 100 days after trasplant of any grade. - Grade of acute graft vs. host disease (aGvHD), according to the “Consensus Conference on Acute GVHD Grading” until 100 days after trasplant. - Chronic graft vs. host disease (cGvHD) by 100 days after trasplant to the end of follow up. - Grade of chronic graft vs. host disease (aGvHD), according to “National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: Diagnosis and staging working group” report by 100 days after trasplant to the end of follow up. - EBV reactivation expressed like positive PCR, exceeding 50 copies/105 cells, in the three different treatment arms until 365 days after transplant.;Timepoint(s) of evaluation of this end point: 1 year | — |
Countries
Italy
Contacts
Public ContactEMATOLOGIA e TMO
Fondazione San Raffaele
Outcome results
None listed