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

Sponsor
IRCCS San Raffaele (Other)
Overall Status
Unknown status
CT.gov ID
NCT00598624
Collaborator
(none)
175
Enrollment
12
Locations
1
Arm
63
Duration (Months)
14.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Treosulfan IV
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
175 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Sep 1, 2005
Anticipated Primary Completion Date :
Dec 1, 2009
Anticipated Study Completion Date :
Dec 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: A

Drug: Treosulfan IV
Treosulfan i.v.: 14 g/m²/d from day -6 to day -4

Outcome Measures

Primary Outcome Measures

  1. Efficacy: Evaluation of engraftment [28 days]

  2. Safety: Evaluation of the incidence of CTC grade 3 and 4 adverse events [between day -6 and day +28]

Secondary Outcome Measures

  1. Efficacy: Evaluation of disease free survival (DFS) [1 year]

  2. Efficacy: Evaluation of overall survival (OS) [1 year]

  3. Efficacy: Evaluation of relapse incidence (RI) [1 year]

  4. Efficacy: Documentation of donor chimerism [on day +28, +56 and +100]

  5. Safety: Evaluation of incidence of non-relapse mortality (NRM) [on day +28 and day +100]

  6. Safety: cumulative incidence of NRM [1 year]

  7. Safety: Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD) [1 year]

  8. Safety: EBV reactivation [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 69 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. 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.

  1. identity between the 2 CB units and the recipient;

  2. Two identical CB units with one or two mismatches with the recipient;

  3. 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.

  1. 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

  1. Age > 18 and < 70 years

  2. Karnofsky Index > 80 %

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

  4. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Ematologia, Ospedale Casa Sollievo della Sofferenza San Giovanni Rotondo Foggia Italy
2 IRCCS San Raffaele; Unità Operativa di Ematologia Milano MI Italy 20100
3 USC Ematologia, Ospedali Riuniti Bergamo Italy
4 Ospedale centrale di Bolzano - Reparto di Ematologia Bolzano Italy
5 PO "R.Binaghi" - CTMO Cagliari Italy
6 AO "Santa Croce" e Carle - Reparto di Ematologia Cuneo Italy
7 Istituto Europeo di Oncologia - Divisione di Ematologia Milano Italy
8 Ospedale Civile - UTI ematologia per il trapianto emopoietico Pescara Italy
9 Arcispedale Santa Maria Nuova - SC di Ematologia Reggio Emilia Italy
10 Dipartimento Biotecnologie Cellulari ed Ematologia; Azienda Policlinico Umberto I Roma Italy 00100
11 AO San Camillo Forlanini - UOC ematologia e trapianto Roma Italy
12 AOU Santa Maria della Misericordia - Clinica Ematologica Udine Italy

Sponsors and Collaborators

  • IRCCS San Raffaele

Investigators

  • Study Director: Fabio FC Ciceri, MD,

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
, ,
ClinicalTrials.gov Identifier:
NCT00598624
Other Study ID Numbers:
  • 2005-005182-11
First Posted:
Jan 22, 2008
Last Update Posted:
Aug 11, 2009
Last Verified:
Aug 1, 2009
Additional relevant MeSH terms:
Lymphoma
Leukemia
Multiple Myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Treosulfan

Study Results

No Results Posted as of Aug 11, 2009