Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Haematological Malignancies

IRCCS San Raffaele12 sites in 1 country175 target enrollmentSeptember 2005

ConditionsLeukemia Chronic Myeloid Leukemia Myelodysplastic Syndrome Diffuse Large Cell Lymphoma Hodgkin Lymphoma Chronic Lymphocytic Leukemia Multiple Myeloma

InterventionsTreosulfan IV

DrugsTreosulfan IV

Overview

Phase: Phase 2
Intervention: Treosulfan IV
Conditions: Leukemia
Sponsor: IRCCS San Raffaele
Enrollment: 175
Locations: 12
Primary Endpoint: Efficacy: Evaluation of engraftment
Last Updated: 16 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicentric, non-randomized, non-controlled open-label phase II trial to evaluate the safety and efficacy of treosulfan in a combination regimen with fludarabine as conditioning therapy prior to allogeneic stem cell transplantation (SCT) in patients with haematological malignancies.

The aim is to demonstrate a clinical benefit compared with historical data on intravenous busulfan (BusulfexTM, BusilvexTM), the only drug so far registered in the indication conditioning before allogeneic stem cell transplantation.

Registry

clinicaltrials.gov

Start Date

September 2005

End Date

December 2010

Last Updated

16 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

IRCCS San Raffaele

Eligibility Criteria

Inclusion Criteria

•Patients with haematological malignancies, according to WHO classification, such as:
•acute myeloid leukaemia -AML- in CR1 except "low-risk cases" defined by t(15;17), t(8;21), inv 16 or normal cytogenetics at diagnosis with FLT3-ITD negative and NPM-1 positive, with no 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

Exclusion Criteria

•Secondary malignancies
•Previous allogeneic transplantation
•Hematopoietic cell transplantation-specific comorbidity index \> 4 (HCT-CI Sorror et al, Appendix M)
•Known and manifested malignant involvement of the CNS
•Active infectious disease
•HIV- positivity or active hepatitis infection
•Impaired liver function (Bilirubin \> upper normal limit; Transaminases \> 3.0 x upper normal limit)
•Impaired renal function (Creatinine-clearance \< 60 ml/min; Serum Creatinine \> 1.5 x upper normal limit).
•Pleural effusion or ascites \> 1.0 L
•Pregnancy or lactation

Arms & Interventions

A

Intervention: Treosulfan IV

Outcomes

Primary Outcomes

Efficacy: Evaluation of engraftment

Time Frame: 28 days

Safety: Evaluation of the incidence of CTC grade 3 and 4 adverse events

Time Frame: between day -6 and day +28

Secondary Outcomes

Efficacy: Evaluation of disease free survival (DFS)(1 year)
Efficacy: Evaluation of overall survival (OS)(1 year)
Efficacy: Evaluation of relapse incidence (RI)(1 year)
Efficacy: Documentation of donor chimerism(on day +28, +56 and +100)
Safety: Evaluation of incidence of non-relapse mortality (NRM)(on day +28 and day +100)
Safety: cumulative incidence of NRM(1 year)
Safety: Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD)(1 year)
Safety: EBV reactivation(1 year)