Hematologic malignancies treated by reduced-intensity conditioning allogeneic transplants. MedDRA version: 18.0 Level: PT Classification code 10001756 Term: Allogenic bone marrow transplantation therapy System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 18.0 Level: LLT Classification code 10018799 Term: GVHD System Organ Class: 100000004870
Conditions
Interventions
Trade Name: Rapamune
Pharmaceutical Form: Tablet
Trade Name: CELLCEPT
Pharmaceutical Form: Tablet
Sponsors
CHU de Liege
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Hematological malignancies confirmed histologically and not rapidly progressing: - AML in CR (defined as = 5% marrow blasts and absence of blasts in the peripheral blood); - MDS with = 5% marrow blasts and absence of blasts in the peripheral blood; - CML in CP; - MPS not in blast crisis and not with extensive marrow fibrosis, - ALL in CR; - Multiple myeloma not rapidly progressing; - CLL; - Non-Hodgkin’s lymphoma (aggressive NHL should have chemosensitive disease); - Hodgkin’s disease with chemosensitive disease. Clinical situations: •Theoretical indication for a standard allo-transplant, but not feasible because: - Age > 50 yrs; - Unacceptable end organ performance; - At the physician’s decision; - Patient’s refusal. •Indication for a standard auto-transplant: -perform mini-allotransplantation 2-6 months after standard autotransplant. •Other inclusion criteria -Male or female; fertile patients must use a reliable contraception method; -Age =75 yrs (children of any age are allowed in the protocol); -Informed consent given by patient or his/her guardian if of minor age. Are the trial subjects under 18? no Number of subjects for this age range: 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
Exclusion criteria
Exclusion criteria: •Any condition not fulfilling inclusion criteria; •HIV positive; •Non-hematological malignancy(ies) (except non-melanoma skin cancer) 3 mg/dL, and symptomatic biliary disease; •Uncontrolled infection; •Karnofsky Performance Score <70%; •Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment; •Patient is a female who is pregnant or breastfeeding; •Any condition precluding the use of sirolimus or MMF.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The present project aims at comparing two postgrafting immunosuppressive regimens (Tac+MMF vs Tac+Sirolimus) after Flu-TBI or Flu-Bu-ATG. The hypothesis is that the Tac+Sirolimus regimen will be associated with better progression-free survival (due to a lower incidence of relapse/progression).To compare for 1-year progression-free survival between the 2 arms in the whole group of patients and separately in those conditioned with Flu-TBI or Flu-Bu-ATG. Following the interim analysis of October 2014, the protocol has been amended to allow inclusion only after Flu-TBI conditioning since November the 3rd, 2014.;Secondary Objective: Comparing 1.relapse rate, nonrelapse mortality, and OS in the 2 arms 1, 2 and 5 years after HSCT in all the patients and separately in those conditioned with Flu-TBI or Flu-Bu-ATG. 2.PFS in the 2 arms 2 and 5 years after HSCT, in all the patients and separately in those with Flu-TBI or Flu-Bu-ATG. 3.hematopoietic engraftment; evaluation 1-year of graft rejection in the 2 arms, in all the patients and separately in those with Flu-TBI or Flu-Bu-ATG. 4.6-mo of grades II-IV and III-IV acute GVHD in the 2 arms, in all the patients and separately in those with Flu-TBI or Flu-Bu-ATG. 5.1-yr of chronic GVHD in the 2 arms, in all the patients and separately in those with Flu-TBI or Flu-Bu-ATG. 6.quality and timing of immunologic reconstitution in the 2 arms, in all the patients and separately in those with Flu-TBI or Flu-Bu-ATG. 7.1-yr infections in the 2 arms, in all the patients and separately in those with Flu-TBI or Flu-Bu-ATG ;Primary end point(s): Comparing the 1-year progression-free survival between the Tracolimus plus Mycophenolate Mofetil arm and the Tracolimus plus Sirolimus arm in the whole group of patients and separately in those conditioned with Flu-TBI or Flu-Bu-ATG before grafting. ;Timepoint(s) of evaluation of this end point: 100 and 180 days post-engraftment. The evaluation will continue the 2, 3, 4 and 5 year afte | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): All the following comparisons will be done in the 2 arms, in the whole group of patients and separately in those conditioned with Flu-TBI or Flu-Bu-ATG: 1-Comparing relapse rate, nonrelapse mortality, and overall survival 1, 2 and 5 years after HSCT. 2-Comparing progression-free survival 2 and 5 years after HSCT. 3-Comparing hematopoietic (whole blood and T cell chimerism) engraftment and to evaluate the 1-year incidence of graft rejection. 4-Comparing the 6-mo incidence of grades II-IV and III-IV acute GVHD. 5-Comparing the 1-yr incidence of chronic GVHD.. 6-Comparing the quality and timing of immunologic reconstitution. 7- Comparing the 1-yr incidences of bacterial, fungal and viral infections. ;Timepoint(s) of evaluation of this end point: Evaluation of engraftment: a) peripheral blood : -Days 28, 42, 60, 100, 180 and 365 post-transplant : whole blood and CD3+ cells. b) whole bone marrow : -Days 42, 100, 180 and 365 post-transplant. | — |
Countries
Belgium
Outcome results
None listed