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

August 10, 2009 updated by: IRCCS San Raffaele

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

175

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Bergamo, Italy
      • Bolzano, Italy
        • Recruiting
        • Ospedale centrale di Bolzano - Reparto di Ematologia
        • Contact:
        • Principal Investigator:
          • Enrico Morello, MD
      • Cagliari, Italy
        • Recruiting
        • PO "R.Binaghi" - CTMO
        • Contact:
        • Principal Investigator:
          • Giorgio La Nasa, MD
      • Cuneo, Italy
        • Recruiting
        • AO "Santa Croce" e Carle - Reparto di Ematologia
        • Contact:
      • Milano, Italy
        • Recruiting
        • Istituto Europeo di Oncologia - Divisione di Ematologia
        • Contact:
      • Pescara, Italy
        • Recruiting
        • Ospedale Civile - UTI ematologia per il trapianto emopoietico
        • Contact:
        • Principal Investigator:
          • Paolo Di Bartolomei, MD
      • Reggio Emilia, Italy
      • Roma, Italy, 00100
        • Recruiting
        • Dipartimento Biotecnologie Cellulari ed Ematologia; Azienda Policlinico Umberto I
        • Contact:
        • Contact:
        • Principal Investigator:
          • Roberto Foa, MD
      • Roma, Italy
        • Recruiting
        • AO San Camillo Forlanini - UOC ematologia e trapianto
        • Contact:
        • Principal Investigator:
          • Ignazio Majolino, MD
      • Udine, Italy
        • Recruiting
        • AOU Santa Maria della Misericordia - Clinica Ematologica
        • Contact:
        • Principal Investigator:
          • Michela Cerno, MD
    • Foggia
    • MI
      • Milano, MI, Italy, 20100
        • Recruiting
        • IRCCS San Raffaele; Unità Operativa di Ematologia
        • Contact:
          • Alessandro Crotta, MD
          • Phone Number: +39 0226433903
          • Email: a.crotta@hsr.it
        • Contact:
        • Principal Investigator:
          • Jacopo Peccatori, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 69 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: A
Drug: Treosulfan IV
Treosulfan i.v.: 14 g/m²/d from day -6 to day -4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy: Evaluation of engraftment
Time Frame: 28 days
28 days
Safety: Evaluation of the incidence of CTC grade 3 and 4 adverse events
Time Frame: between day -6 and day +28
between day -6 and day +28

Secondary Outcome Measures

Outcome Measure
Time Frame
Efficacy: Evaluation of disease free survival (DFS)
Time Frame: 1 year
1 year
Efficacy: Evaluation of overall survival (OS)
Time Frame: 1 year
1 year
Efficacy: Evaluation of relapse incidence (RI)
Time Frame: 1 year
1 year
Efficacy: Documentation of donor chimerism
Time Frame: on day +28, +56 and +100
on day +28, +56 and +100
Safety: Evaluation of incidence of non-relapse mortality (NRM)
Time Frame: on day +28 and day +100
on day +28 and day +100
Safety: cumulative incidence of NRM
Time Frame: 1 year
1 year
Safety: Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD)
Time Frame: 1 year
1 year
Safety: EBV reactivation
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Investigators

  • Study Director: Fabio FC Ciceri, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (ANTICIPATED)

December 1, 2009

Study Completion (ANTICIPATED)

December 1, 2010

Study Registration Dates

First Submitted

January 10, 2008

First Submitted That Met QC Criteria

January 21, 2008

First Posted (ESTIMATE)

January 22, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

August 11, 2009

Last Update Submitted That Met QC Criteria

August 10, 2009

Last Verified

August 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005-005182-11

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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