Clinical phase II trial to evaluate the safety and efficacy of clofarabine and treosulfan conditioning prior to peripheral blood stem cells transplantation in paediatric and adult patients with advanced haematological malignancies - ND

• Conditions: patients affected by advanced haematological malignancies; MedDRA version: 9.1Level: HLGTClassification code 10018865Term: Haematopoietic neoplasms (excl leukaemias and lymphomas)

• Registration Number: EUCTR2008-006972-31-IT
• Lead Sponsor: OSPEDALE S. RAFFAELE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-12
• Last Update Posted: 12 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Patients with haematological malignancies such as
- acute myeloid leukaemia -AML- beyond CR1
- acute lymphoblast leukaemia -ALL- beyond CR1
- chronic myeloid leukaemia -CML- beyond chronic phase (CP1)
- myelodysplastic syndrome -MDS- such as RCMD, RAEB1 and RAEB2

Availability of a
-HLA-identical sibling donor (MRD) or
-HLA-identical unrelated donor (MUD) with HLA-identity defined by the following markers: A and B at antigenic level; DRB1 at allelic level. However every patient and donor will be typed at allelic level at HLA-A, B, C, DRB1, DQB1. If no class I and class II completely identical donor (i.e. 10 out of 10) can be identified, no more than two allele disparity between patient and donor is acceptable. The target graft size (unmanipulated) will be: 4 - 10 x 106 CD34+ cells/kg BW recipient
Have adequate renal and hepatic functions as indicated by the following laboratory values:
Pediatric Population: Calculated creatinine clearance ≥ 90 ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys.
Adult Population: Serum creatinine 1.0 mg/dL; if serum creatinine 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black.
Serum bilirubin ≤1.5 × upper limit of normal (ULN)
Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 × ULN
Alkaline phosphatase  2.5 × ULN

Karnofsky Index > 80 %
Age > 1 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:
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

1.Secondary malignancies
2.Previous allogeneic transplantation
3.Hematopoietic cell transplantation-specific comorbidity index (HCT-CI > 4 (Sorror et al Appendix M)
1.Secondary malignancies
2.Previous allogeneic transplantation
3.Hematopoietic cell transplantation-specific comorbidity index (HCT-CI > 4 (Sorror et al Appendix M)
4.HIV- positivity or active hepatitis infection

5.Pleural effusion or ascites > 1.0 L
6.Pregnancy or lactation
7.Known hypersensitivity to treosulfan and/or clofarabine
8.Participation in another experimental drug trial within 4 weeks before day -6
9.Non-cooperative behaviour or non-compliance
10.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: -Evaluation of cumulative incidence non-relapse mortality (NRM) on day +100;Secondary Objective: Efficacy<br>-Evaluation of engraftment <br>-Evaluation of progression free survival (PFS) <br>-Evaluation of overall survival (OS)<br>-Evaluation of relapse incidence (RI)<br>-Documentation of donor chimerism on day +28, +56 and +100<br><br>Safety<br>-Evaluation of incidence of non-relapse mortality (NRM) on day +28 and +360 <br>-Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD).<br>-EBV reactivation;Primary end point(s): evaluation of safety by cumulative incidence of NRM at day +100