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 because the information has not been verified recently.
Verified August 2009 by IRCCS San Raffaele.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT00598624
First received: January 10, 2008
Last updated: August 10, 2009
Last verified: August 2009
  Purpose

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
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
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

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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 ClinicalTrials.gov identifier: NCT00598624

Contacts
Contact: Luciano LC Callegaro, Monitor +390226433903 callegaro.luciano@hsr.it
Contact: Stefania ST Trinca, Data Manager +390226433903 trinca.stefania@hsr.it

Locations
Italy
Ematologia, Ospedale Casa Sollievo della Sofferenza Recruiting
San Giovanni Rotondo, Foggia, Italy
Contact: Angelo Michele Carella, MD       am.carella@operapadrepio.it   
Contact: Marzia Tricarico, DM       m.tricarico@operapadrepio.it   
Principal Investigator: Nicola Cascavilla, MD         
IRCCS San Raffaele; Unità Operativa di Ematologia Recruiting
Milano, MI, Italy, 20100
Contact: Alessandro Crotta, MD    +39 0226433903    a.crotta@hsr.it   
Contact: Stefania Trinca    +39 0226434289    stefania.trinca@hsr.it   
Principal Investigator: Jacopo Peccatori, MD         
USC Ematologia, Ospedali Riuniti Recruiting
Bergamo, Italy
Contact: Anna Grassi, MD       agrassi@ospedaliriuniti.bergamo.it   
Contact: Maria Luisa Ferrari, DM       mlferrari@ospedaliriuniti.bergamo.it   
Principal Investigator: Alessandro Rambaldi, MD         
Ospedale centrale di Bolzano - Reparto di Ematologia Recruiting
Bolzano, Italy
Contact: Enrico Morello, MD    +390471908807    enrico.morello@asbz.it   
Principal Investigator: Enrico Morello, MD         
PO "R.Binaghi" - CTMO Recruiting
Cagliari, Italy
Contact: Adriana Vacca, MD    +393285452813    vaadriana@tiscali.it   
Principal Investigator: Giorgio La Nasa, MD         
AO "Santa Croce" e Carle - Reparto di Ematologia Recruiting
Cuneo, Italy
Contact: Laura Bertolotti, Data Manager    +390171642229    laura.bertolotti@libero.it   
Principal Investigator: Andrea Gallamini, MD         
Istituto Europeo di Oncologia - Divisione di Ematologia Recruiting
Milano, Italy
Contact: Liliana Calabrese, Data Manager    +390257489536    liliana.calabrese@ieo.it   
Principal Investigator: Giovanni Martinelli, MD         
Ospedale Civile - UTI ematologia per il trapianto emopoietico Recruiting
Pescara, Italy
Contact: Paolo Di Bartolomei, MD       pescaratmo@virgilio.it   
Principal Investigator: Paolo Di Bartolomei, MD         
Arcispedale Santa Maria Nuova - SC di Ematologia Recruiting
Reggio Emilia, Italy
Contact: Alessandro Bonini, MD       bonini.alessandro@asmn.re.it   
Principal Investigator: Luigi Gugliotta, MD         
Dipartimento Biotecnologie Cellulari ed Ematologia; Azienda Policlinico Umberto I Recruiting
Roma, Italy, 00100
Contact: Emilia Iannella, MD    +39 3202233365    emiliaiannella@libero.it   
Contact: Roberto Ricci    +39 3477578735    r.ricci@bce.uniroma1.it   
Principal Investigator: Roberto Foa, MD         
AO San Camillo Forlanini - UOC ematologia e trapianto Recruiting
Roma, Italy
Contact: Beatrice Pinazzi, MD       mpinazzi@scamilloforlanini.rm.it   
Principal Investigator: Ignazio Majolino, MD         
AOU Santa Maria della Misericordia - Clinica Ematologica Recruiting
Udine, Italy
Contact: Francesca Patriarca, MD       patriarca.francesca@aoud.sanita.fvg.it   
Principal Investigator: Michela Cerno, MD         
Sponsors and Collaborators
IRCCS San Raffaele
Investigators
Study Director: Fabio FC Ciceri, MD
  More Information

No publications provided

Responsible Party: Fabio Ciceri, MD, IRCCS San Raffaele
ClinicalTrials.gov 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:
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Precancerous Conditions

ClinicalTrials.gov processed this record on August 27, 2014