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

NCT ID: NCT00598624

Last Updated: 2009-08-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-09-30

Study Completion Date

2010-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Leukemia Chronic Myeloid Leukemia Myelodysplastic Syndrome Diffuse Large Cell Lymphoma Hodgkin Lymphoma Chronic Lymphocytic Leukemia Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A

Group Type EXPERIMENTAL

Treosulfan IV

Intervention Type DRUG

Treosulfan i.v.: 14 g/m²/d from day -6 to day -4

Interventions

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Treosulfan IV

Treosulfan i.v.: 14 g/m²/d from day -6 to day -4

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IRCCS San Raffaele

OTHER

Sponsor Role lead

Responsible Party

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IRCCS San Raffaele

Principal Investigators

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Fabio FC Ciceri, MD

Role: STUDY_DIRECTOR

Locations

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Ematologia, Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Site Status RECRUITING

IRCCS San Raffaele; Unità Operativa di Ematologia

Milan, MI, Italy

Site Status RECRUITING

Dipartimento Biotecnologie Cellulari ed Ematologia; Azienda Policlinico Umberto I

Roma, Roma, Italy

Site Status RECRUITING

USC Ematologia, Ospedali Riuniti

Bergamo, , Italy

Site Status RECRUITING

Ospedale centrale di Bolzano - Reparto di Ematologia

Bolzano, , Italy

Site Status RECRUITING

PO "R.Binaghi" - CTMO

Cagliari, , Italy

Site Status RECRUITING

AO "Santa Croce" e Carle - Reparto di Ematologia

Cuneo, , Italy

Site Status RECRUITING

Istituto Europeo di Oncologia - Divisione di Ematologia

Milan, , Italy

Site Status RECRUITING

Ospedale Civile - UTI ematologia per il trapianto emopoietico

Pescara, , Italy

Site Status RECRUITING

Arcispedale Santa Maria Nuova - SC di Ematologia

Reggio Emilia, , Italy

Site Status RECRUITING

AO San Camillo Forlanini - UOC ematologia e trapianto

Roma, , Italy

Site Status RECRUITING

AOU Santa Maria della Misericordia - Clinica Ematologica

Udine, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Luciano LC Callegaro, Monitor

Role: CONTACT

+390226433903

Stefania ST Trinca, Data Manager

Role: CONTACT

+390226433903

Facility Contacts

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Angelo Michele Carella, MD

Role: primary

Marzia Tricarico, DM

Role: backup

Alessandro Crotta, MD

Role: primary

+39 0226433903

Stefania Trinca

Role: backup

+39 0226434289

Emilia Iannella, MD

Role: primary

+39 3202233365

Roberto Ricci

Role: backup

+39 3477578735

Anna Grassi, MD

Role: primary

Maria Luisa Ferrari, DM

Role: backup

Enrico Morello, MD

Role: primary

+390471908807

Adriana Vacca, MD

Role: primary

+393285452813

Laura Bertolotti, Data Manager

Role: primary

+390171642229

Liliana Calabrese, Data Manager

Role: primary

+390257489536

Paolo Di Bartolomei, MD

Role: primary

Alessandro Bonini, MD

Role: primary

Beatrice Pinazzi, MD

Role: primary

Francesca Patriarca, MD

Role: primary

References

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Lazzari L, Ruggeri A, Lupo Stanghellini MT, Mastaglio S, Messina C, Giglio F, Lorusso A, Perini T, Piemontese S, Marcatti M, Lorentino F, Xue E, Clerici D, Corti C, Bernardi M, Assanelli A, Greco R, Ciceri F, Peccatori J. Treosulfan-Based Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation: Long-Term Results From a Phase 2 Clinical Trial. Front Oncol. 2021 Sep 10;11:731478. doi: 10.3389/fonc.2021.731478. eCollection 2021.

Reference Type DERIVED
PMID: 34568066 (View on PubMed)

Other Identifiers

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2005-005182-11

Identifier Type: -

Identifier Source: org_study_id

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