Clinical Trials Logo

Clinical Trial Details — Status: Unknown status

Administrative data

NCT number NCT00598624
Other study ID # 2005-005182-11
Secondary ID
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
Health authority
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

Study Design


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
See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1