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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00598624
Recruitment Status : Unknown
Verified August 2009 by IRCCS San Raffaele.
Recruitment status was:  Recruiting
First Posted : January 22, 2008
Last Update Posted : August 11, 2009
Information provided by:
IRCCS San Raffaele

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
Leukemia Chronic Myeloid Leukemia Myelodysplastic Syndrome Diffuse Large Cell Lymphoma Hodgkin Lymphoma Chronic Lymphocytic Leukemia Multiple Myeloma Drug: Treosulfan IV Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 2005
Estimated Primary Completion Date : December 2009
Estimated Study Completion Date : December 2010

Arm Intervention/treatment
Experimental: A Drug: Treosulfan IV
Treosulfan i.v.: 14 g/m²/d from day -6 to day -4

Primary Outcome Measures :
  1. Efficacy: Evaluation of engraftment [ Time Frame: 28 days ]
  2. Safety: Evaluation of the incidence of CTC grade 3 and 4 adverse events [ Time Frame: between day -6 and day +28 ]

Secondary Outcome Measures :
  1. Efficacy: Evaluation of disease free survival (DFS) [ Time Frame: 1 year ]
  2. Efficacy: Evaluation of overall survival (OS) [ Time Frame: 1 year ]
  3. Efficacy: Evaluation of relapse incidence (RI) [ Time Frame: 1 year ]
  4. Efficacy: Documentation of donor chimerism [ Time Frame: on day +28, +56 and +100 ]
  5. Safety: Evaluation of incidence of non-relapse mortality (NRM) [ Time Frame: on day +28 and day +100 ]
  6. Safety: cumulative incidence of NRM [ Time Frame: 1 year ]
  7. Safety: Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD) [ Time Frame: 1 year ]
  8. Safety: EBV reactivation [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
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
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00598624

Contact: Luciano LC Callegaro, Monitor +390226433903
Contact: Stefania ST Trinca, Data Manager +390226433903

Ematologia, Ospedale Casa Sollievo della Sofferenza Recruiting
San Giovanni Rotondo, Foggia, Italy
Contact: Angelo Michele Carella, MD   
Contact: Marzia Tricarico, DM   
Principal Investigator: Nicola Cascavilla, MD         
IRCCS San Raffaele; Unità Operativa di Ematologia Recruiting
Milano, MI, Italy, 20100
Contact: Alessandro Crotta, MD    +39 0226433903   
Contact: Stefania Trinca    +39 0226434289   
Principal Investigator: Jacopo Peccatori, MD         
USC Ematologia, Ospedali Riuniti Recruiting
Bergamo, Italy
Contact: Anna Grassi, MD   
Contact: Maria Luisa Ferrari, DM   
Principal Investigator: Alessandro Rambaldi, MD         
Ospedale centrale di Bolzano - Reparto di Ematologia Recruiting
Bolzano, Italy
Contact: Enrico Morello, MD    +390471908807   
Principal Investigator: Enrico Morello, MD         
PO "R.Binaghi" - CTMO Recruiting
Cagliari, Italy
Contact: Adriana Vacca, MD    +393285452813   
Principal Investigator: Giorgio La Nasa, MD         
AO "Santa Croce" e Carle - Reparto di Ematologia Recruiting
Cuneo, Italy
Contact: Laura Bertolotti, Data Manager    +390171642229   
Principal Investigator: Andrea Gallamini, MD         
Istituto Europeo di Oncologia - Divisione di Ematologia Recruiting
Milano, Italy
Contact: Liliana Calabrese, Data Manager    +390257489536   
Principal Investigator: Giovanni Martinelli, MD         
Ospedale Civile - UTI ematologia per il trapianto emopoietico Recruiting
Pescara, Italy
Contact: Paolo Di Bartolomei, MD   
Principal Investigator: Paolo Di Bartolomei, MD         
Arcispedale Santa Maria Nuova - SC di Ematologia Recruiting
Reggio Emilia, Italy
Contact: Alessandro Bonini, MD   
Principal Investigator: Luigi Gugliotta, MD         
Dipartimento Biotecnologie Cellulari ed Ematologia; Azienda Policlinico Umberto I Recruiting
Roma, Italy, 00100
Contact: Emilia Iannella, MD    +39 3202233365   
Contact: Roberto Ricci    +39 3477578735   
Principal Investigator: Roberto Foa, MD         
AO San Camillo Forlanini - UOC ematologia e trapianto Recruiting
Roma, Italy
Contact: Beatrice Pinazzi, MD   
Principal Investigator: Ignazio Majolino, MD         
AOU Santa Maria della Misericordia - Clinica Ematologica Recruiting
Udine, Italy
Contact: Francesca Patriarca, MD   
Principal Investigator: Michela Cerno, MD         
Sponsors and Collaborators
IRCCS San Raffaele
Study Director: Fabio FC Ciceri, MD

Responsible Party: Fabio Ciceri, MD, IRCCS San Raffaele Identifier: NCT00598624     History of Changes
Other Study ID Numbers: 2005-005182-11
First Posted: January 22, 2008    Key Record Dates
Last Update Posted: August 11, 2009
Last Verified: August 2009

Additional relevant MeSH terms:
Multiple Myeloma
Myelodysplastic Syndromes
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Leukemia, B-Cell
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Leukemia, Myeloid