Clinical Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation (HSCT)

• Status: Unknown status
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IRCCS San Raffaele
• Treatments: Busulfan; Treosulfan

Criteria

Inclusion Criteria:

1. 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

• 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

2. Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD)

• HLA-identity defined by the following markers: A, B, DRB1, DQB1 or a single or double Cord Blood unit (CB) with at least a 4 out of 6 HLA-matching by the following markers: A, B and DRB.

A) identity between the 2 CB units and the recipient;

B) Two identical CB units with one or two mismatches with the recipient;

C) Two CB units with one mismatch between them and two mismatches with the recipient. We will prefer mismatches either for class I or for class II antigens; we will avoid mismatches concerning both classes I and II together.

3. Target graft size (unmanipulated, preferably not cryopreserved)

• bone marrow: 2 to 10 x 106 CD34+ cells/kg BW recipient or > 2 x 108 nucleated cells/kg BW recipient or

• peripheral blood: 4 to 10 x 106 CD34+ cells/kg BW recipient

4. Age > 18 and < 70 years

5. Karnofsky Index > 80 %

6. Adequate contraception in female patients of child-bearing potential

7. Written informed consent

Exclusion Criteria:

1. Secondary malignancies

2. Previous allogeneic transplantation

3. Hematopoietic cell transplantation-specific comorbidity index > 4 (HCT-CI Sorror et al, Appendix M)

4. Known and manifested malignant involvement of the CNS

5. Active infectious disease

6. HIV- positivity or active hepatitis infection

7. Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)

8. Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).

9. Pleural effusion or ascites > 1.0 L

10. Pregnancy or lactation

11. Known hypersensitivity to treosulfan and/or fludarabine

12. Participation in another experimental drug trial within 4 weeks before day -6

13. Non-co-operative behaviour or non-compliance

14. Psychiatric diseases or conditions that might impair the ability to give informed consent