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

This study is currently recruiting participants.
Verified by IRCCS San Raffaele, June 2008

Sponsored by: IRCCS San Raffaele
Information provided by: IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT00598624
  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 II

Genetics Home Reference related topics:   aceruloplasminemia    hemophilia   

MedlinePlus related topics:   Cancer    Hodgkin's Disease    Leukemia, Adult Acute    Leukemia, Adult Chronic    Lymphoma    Multiple Myeloma   

ChemIDplus related topics:   Treosulfan   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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

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:   September 2009
Estimated Primary Completion Date:   September 2008 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
A: Experimental 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, preferally 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

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
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            
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            
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            
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            
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            
Italy, Foggia
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            
Italy, MI
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            

Sponsors and Collaborators
IRCCS San Raffaele

Investigators
Study Director:     Fabio FC Ciceri, MD     Unaffiliated    
  More Information


Responsible Party:   IRCCS San Raffaele ( Fabio Ciceri, MD )
Study ID Numbers:   2005-005182-11
First Received:   January 10, 2008
Last Updated:   June 16, 2008
ClinicalTrials.gov Identifier:   NCT00598624
Health Authority:   Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Study placed in the following topic categories:
Leukemia, Lymphoid
Hodgkin's disease
Chronic myelogenous leukemia
Precancerous Conditions
Blood Protein Disorders
Hodgkin lymphoma, adult
Paraproteinemias
Hemostatic Disorders
Lymphoma, large-cell
Lymphoma, B-Cell
Leukemia
Preleukemia
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Hematologic Diseases
Blood Coagulation Disorders
Myelodysplasia
Myelodysplastic Syndromes
Myeloproliferative Disorders
Vascular Diseases
Leukemia, Myeloid
Multiple Myeloma
Lymphatic Diseases

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Disease
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on October 10, 2008




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