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

Multiple Myeloma Clinical Trial

— AlloTreo  

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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT00598624
• Other study ID #: 2005-005182-11
• Status: Unknown status
• Phase: Phase 2
• First received: January 10, 2008
• Last updated: August 10, 2009
• Start date: September 2005
• Est. completion date: December 2010

Study information

• Verified date: August 2009
• Source: IRCCS San Raffaele
• Contact: Luciano LC Callegaro, Monitor
• Phone: +390226433903
• Email: callegaro.luciano[@]hsr.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 175
• Est. completion date: December 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Chronic Myeloid Leukemia
• Diffuse Large Cell Lymphoma
• Hodgkin Disease
• Hodgkin Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Multiple Myeloma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

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

Locations

Country	Name	City	State
Italy	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	IRCCS San Raffaele; Unità Operativa di Ematologia	Milano	MI
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	AO San Camillo Forlanini - UOC ematologia e trapianto	Roma
Italy	Dipartimento Biotecnologie Cellulari ed Ematologia; Azienda Policlinico Umberto I	Roma
Italy	Ematologia, Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Italy	AOU Santa Maria della Misericordia - Clinica Ematologica	Udine

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Evaluation of engraftment		28 days
Primary	Safety: Evaluation of the incidence of CTC grade 3 and 4 adverse events		between day -6 and day +28
Secondary	Efficacy: Evaluation of disease free survival (DFS)		1 year
Secondary	Efficacy: Evaluation of overall survival (OS)		1 year
Secondary	Efficacy: Evaluation of relapse incidence (RI)		1 year
Secondary	Efficacy: Documentation of donor chimerism		on day +28, +56 and +100
Secondary	Safety: Evaluation of incidence of non-relapse mortality (NRM)		on day +28 and day +100
Secondary	Safety: cumulative incidence of NRM		1 year
Secondary	Safety: Evaluation of cumulative incidence and severity of acute and chronic graft vs. host disease (GvHD)		1 year
Secondary	Safety: EBV reactivation		1 year