Treosulfan Based Conditioning Acute Myeloid Leukaemia (AML)
Primary Purpose
Acute Myeloid Leukaemia
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Treosulfan
Sponsored by
About this trial
This is an interventional supportive care trial for Acute Myeloid Leukaemia focused on measuring Treosulfan, Fludarabine, ATG, AML
Eligibility Criteria
Inclusion Criteria:
- Patients with acute myeloid leukaemia (AML) according to WHO classification (> 20% myeloblasts in peripheral blood or bone marrow at initial diagnosis) with < 5% myeloblast in the bone marrow, indicated for allogeneic transplantation
- 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.
- Target graft size (unmanipulated)
- bone marrow: 2 - 10 x 106 CD34+ cells/kg BW recipient or > 2 x 108 nucleated cells/kg BW recipient or
- peripheral blood: 4 - 10 x 106 CD34+ cells/kg BW recipient
- Age > 18 and < 60 years
- Karnofsky Index > 80 %
- Adequate contraception in female patients of child-bearing potential
- Written informed consent
Exclusion Criteria:
- Therapy related secondary AML
- AML with t(8;21)(q22;q22) in CR1
- Acute promyelocytic leukaemia with t(15;17)(q22;q12) in CR1
- Secondary malignancies
- Previous allogeneic transplantation
- Severe concomitant illnesses / medical conditions (e.g. impaired respiratory and/or cardiac function)
- Known and manifested malignant involvement of the CNS
- Active infectious disease
- HIV- positivity or active hepatitis infection
- Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)
- Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
- Pleural effusion or ascites > 1.0 L
- Pregnancy or lactation
- Known hypersensitivity to treosulfan and/or fludarabine
- Participation in another experimental drug trial within 4 weeks before day -6
- Non-co-operative behaviour or non-compliance
- Psychiatric diseases or conditions that might impair the ability to give informed consent
Sites / Locations
- University of Rostock
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treosulfan
Arm Description
Patients with acute myeloid leukaemia (AML) according to WHO classification (> 20% myeloblasts in peripheral blood or bone marrow at initial diagnosis) with < 5% myeloblasts in the bone marrow, indicated for allogeneic transplantation
Outcomes
Primary Outcome Measures
Efficacy - Evaluation of engraftment. Safety - Evaluation of the incidence of the following CTC grade 3 and 4 adverse events between day -6 and day +28 - hyperbilirubinemia and mucositis / stomatitis - veno-occlusive disease - seizures
Secondary Outcome Measures
Efficacy - Evaluation of disease free survival (DFS) - Evaluation of overall survival (OS) - Evaluation of relapse incidence (RI) - Donor chimerism on day +28, +56 and +100. Safety - Evaluation of NRM on days +28 and +100
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01063660
Brief Title
Treosulfan Based Conditioning Acute Myeloid Leukaemia (AML)
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 Acute Myeloid Leukaemia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2010
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
medac GmbH
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a multicenter, multinational, 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 AML.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukaemia
Keywords
Treosulfan, Fludarabine, ATG, AML
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treosulfan
Arm Type
Experimental
Arm Description
Patients with acute myeloid leukaemia (AML) according to WHO classification (> 20% myeloblasts in peripheral blood or bone marrow at initial diagnosis) with < 5% myeloblasts in the bone marrow, indicated for allogeneic transplantation
Intervention Type
Drug
Intervention Name(s)
Treosulfan
Other Intervention Name(s)
Ovastat
Intervention Description
14 g/m²/d day -6 to -4
Primary Outcome Measure Information:
Title
Efficacy - Evaluation of engraftment. Safety - Evaluation of the incidence of the following CTC grade 3 and 4 adverse events between day -6 and day +28 - hyperbilirubinemia and mucositis / stomatitis - veno-occlusive disease - seizures
Time Frame
3.5 years
Secondary Outcome Measure Information:
Title
Efficacy - Evaluation of disease free survival (DFS) - Evaluation of overall survival (OS) - Evaluation of relapse incidence (RI) - Donor chimerism on day +28, +56 and +100. Safety - Evaluation of NRM on days +28 and +100
Time Frame
3.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with acute myeloid leukaemia (AML) according to WHO classification (> 20% myeloblasts in peripheral blood or bone marrow at initial diagnosis) with < 5% myeloblast in the bone marrow, indicated for allogeneic transplantation
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.
Target graft size (unmanipulated)
bone marrow: 2 - 10 x 106 CD34+ cells/kg BW recipient or > 2 x 108 nucleated cells/kg BW recipient or
peripheral blood: 4 - 10 x 106 CD34+ cells/kg BW recipient
Age > 18 and < 60 years
Karnofsky Index > 80 %
Adequate contraception in female patients of child-bearing potential
Written informed consent
Exclusion Criteria:
Therapy related secondary AML
AML with t(8;21)(q22;q22) in CR1
Acute promyelocytic leukaemia with t(15;17)(q22;q12) in CR1
Secondary malignancies
Previous allogeneic transplantation
Severe concomitant illnesses / medical conditions (e.g. impaired respiratory and/or cardiac function)
Known and manifested malignant involvement of the CNS
Active infectious disease
HIV- positivity or active hepatitis infection
Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)
Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
Pleural effusion or ascites > 1.0 L
Pregnancy or lactation
Known hypersensitivity to treosulfan and/or fludarabine
Participation in another experimental drug trial within 4 weeks before day -6
Non-co-operative behaviour or non-compliance
Psychiatric diseases or conditions that might impair the ability to give informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathias Freund, MD
Organizational Affiliation
University of Rostock
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Rostock
City
Rostock
ZIP/Postal Code
18057
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
22158386
Citation
Casper J, Holowiecki J, Trenschel R, Wandt H, Schaefer-Eckart K, Ruutu T, Volin L, Einsele H, Stuhler G, Uharek L, Blau I, Bornhaeuser M, Zander AR, Larsson K, Markiewicz M, Giebel S, Kruzel T, Mylius HA, Baumgart J, Pichlmeier U, Freund M, Beelen DW. Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning. Bone Marrow Transplant. 2012 Sep;47(9):1171-7. doi: 10.1038/bmt.2011.242. Epub 2011 Dec 12.
Results Reference
derived
Learn more about this trial
Treosulfan Based Conditioning Acute Myeloid Leukaemia (AML)
We'll reach out to this number within 24 hrs