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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified August 2009 by IRCCS San Raffaele.
Recruitment status was:  Recruiting
Information provided by:
IRCCS San Raffaele Identifier:
First received: January 10, 2008
Last updated: August 10, 2009
Last verified: August 2009

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • Efficacy: Evaluation of engraftment [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Safety: Evaluation of the incidence of CTC grade 3 and 4 adverse events [ Time Frame: between day -6 and day +28 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy: Evaluation of disease free survival (DFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Efficacy: Evaluation of overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Efficacy: Evaluation of relapse incidence (RI) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Efficacy: Documentation of donor chimerism [ Time Frame: on day +28, +56 and +100 ] [ Designated as safety issue: No ]
  • Safety: Evaluation of incidence of non-relapse mortality (NRM) [ Time Frame: on day +28 and day +100 ] [ Designated as safety issue: Yes ]
  • Safety: cumulative incidence of NRM [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Safety: Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Safety: EBV reactivation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 175
Study Start Date: September 2005
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Treosulfan IV
Treosulfan i.v.: 14 g/m²/d from day -6 to day -4


Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
Genders 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00598624

Ematologia, Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Foggia, Italy
IRCCS San Raffaele; Unità Operativa di Ematologia
Milano, MI, Italy, 20100
USC Ematologia, Ospedali Riuniti
Bergamo, Italy
Ospedale centrale di Bolzano - Reparto di Ematologia
Bolzano, Italy
PO "R.Binaghi" - CTMO
Cagliari, Italy
AO "Santa Croce" e Carle - Reparto di Ematologia
Cuneo, Italy
Istituto Europeo di Oncologia - Divisione di Ematologia
Milano, Italy
Ospedale Civile - UTI ematologia per il trapianto emopoietico
Pescara, Italy
Arcispedale Santa Maria Nuova - SC di Ematologia
Reggio Emilia, Italy
Dipartimento Biotecnologie Cellulari ed Ematologia; Azienda Policlinico Umberto I
Roma, Italy, 00100
AO San Camillo Forlanini - UOC ematologia e trapianto
Roma, Italy
AOU Santa Maria della Misericordia - Clinica Ematologica
Udine, Italy
Sponsors and Collaborators
IRCCS San Raffaele
Study Director: Fabio FC Ciceri, MD
  More Information

Responsible Party: Fabio Ciceri, MD, IRCCS San Raffaele Identifier: NCT00598624     History of Changes
Other Study ID Numbers: 2005-005182-11 
Study First Received: January 10, 2008
Last Updated: August 10, 2009
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

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 processed this record on January 18, 2017