Treosulfan-based conditioning and Rapamycin-base GvHD prophylaxis prior to un-manipulated allogeneic haematopoietic stem cell transplantation from a mismatched donor in patients with high risk haematological malignancies
- Conditions
- neoplastic and haematologic patologiesMedDRA version: 14.1Level: PTClassification code 10057677Term: TransplantSystem Organ Class: 10042613 - Surgical and medical proceduresTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2007-005477-54-IT
- Lead Sponsor
- OSPEDALE S. RAFFAELE DI MILANO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
· Patients with haematological 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)- any ALL beyond CR1- chronic myeloid leukaemia -CML- in chronic phase (CP) or accelerated phase (AP) intolerant/not responsive to TK-inhibitors- myeloproliferative disorders -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- CLL relapsing after high dose chemotherapy- 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· Lacking of a HLA-identical related (MRD) or unrelated (MUD) donor, eligible to donate· Availability of a mismatched related donor (MMRD) sharing at least one full haplotype or a MUD satisfying the minimum criterion of a 5/6 antigen match at HLA-A, -B and -DRB1 · Target graft size (unmanipulated)- peripheral blood: 4 - 10 x 106 CD34+ cells/kg BW recipient - bone marrow: 2 - 10 x 106 CD34+ cells/kg BW recipient or > 2 x 108 nucleated cells/kg BW recipient or· Karnofsky Index > 80 % · Age > 0 and < 70 years· Adequate contraception in female patients of child-bearing potential · Written informed consent
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Secondary malignancies2. A hematopoietic cell transplantation-specific comorbidity index (Sorror et al Appendix B) > 43. Known and manifested malignant involvement of the CNS 4. Active infectious disease 5. Active HIV, HBV or HCV infection6. Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)7. Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).8. Pleural effusion or ascites > 1.0 L 9. Pregnancy or lactation10. Known hypersensitivity to treosulfan and/or fludarabine and/or rapamycin11. Participation in another experimental drug trial within 4 weeks before day -612. Non-co-operative behaviour or non-compliance 13. Psychiatric diseases or conditions that might impair the ability to give informed consent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Safety- Evaluation of cumulative incidence non-relapse mortality (NRM) on day +100;Secondary Objective: Efficacy- Evaluation of engraftment - Evaluation of progression free survival (PFS) - Evaluation of overall survival (OS)- Evaluation of relapse incidence (RI)- Documentation of donor chimerism on day +28, +56 and +100Safety- Evaluation of incidence of non-relapse mortality (NRM) on day +28 and +360 - Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD).- EBV reactivation;Primary end point(s): Safety- Evaluation of cumulative incidence non-relapse mortality (NRM) on day +100;Timepoint(s) of evaluation of this end point: day +100
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Safety- Evaluation of cumulative incidence non-relapse mortality (NRM) on day +100;Timepoint(s) of evaluation of this end point: day +100