Dose-range Finding Treosulfan-based Conditioning
- Registration Number
- NCT01063647
- Lead Sponsor
- medac GmbH
- Brief Summary
Evaluation of the safety and efficacy of 3 x 10, 3 x 12 or 3 x 14 g/m² Treosulfan resp., combined with 5 x 30 mg/m² fludarabine prior to allogeneic, hematopoietic stem cell transplantation of patients with hematological malignancies, but non-eligible to standard conditioning treatment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
-
Patients with a haematological chemosensitive malignancy indicated for an allogeneic transplantation, but presenting an increased toxicity risk for classical (high-dose busulfan or standard-dose total body irradiation) conditioning therapies (remission criteria ref. to Appendix L):
- CML in first or subsequent chronic phase
- NHL in 2nd CR/PR, chemosensitive PR after autologous transplantation ; CLL in 2nd or subsequent CR/PR
- Relapsed Morbus Hodgkin (MH) after autologous transplantation
- Multiple Myeloma (MM) stage II and III according to Durie and Salmon
- AML in 2nd CR/PR or high-risk AML in 1st CR/PR
High-risk defined for example by the following:
- Cytogenetics: -5/5q, -7/7q, del(5q), abnormalities of 3q, complex karyotype (> 3 abnormalities), or
- PR after 1 cycle of induction therapy
- ALL in 2nd CR/PR or high-risk ALL in 1st CR/PR
High-risk defined as follows:
- Leukocytes > 3000/µl (B-Linage) or > 100000/µl (T-Linage);
- Pro-B-ALL, pre-T-ALL
- Cytogenetics: t(9;22)/BCR-ABL; t(4;11)/ALL1-AF
- MDS (patients without prior chemotherapy may be included)
-
Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD) or one mismatch (out of the 6 standard markers) sibling donor (1 misMRD):
• HLA-identity defined by the following markers: A, B, DRB1. DQB1 must be recorded.
-
Age > 18 years
-
Karnofsky Index > 80 %
-
Adequate contraception in female patients of child-bearing potential
-
Co-operative behavior of individual patients
-
Written informed consent
- Completely chemotherapy-resistant disease
- Severe cardiac insufficiency, severe cardio-vascular or other severe concomitant diseases
- Symptomatic malignant involvement of the CNS
- Active infectious disease
- HIV-positive or active hepatitis infection
- Impaired liver function (Bilirubin > 1.5 x 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 fludarabine and/or treosulfan
- Parallel participation in another experimental drug trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 Treosulfan Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4) 1 Treosulfan Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4) 3 Treosulfan Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)
- Primary Outcome Measures
Name Time Method Safety - Evaluation of feasibility and tolerability of 3 x 10, 12 or 14 g/m² Treosulfan combined with 5 x 30 mg/m² fludarabine prior to allogeneic stem cell transplantation • frequency and severity of TRM until 6 months after transplantation 6 months
- Secondary Outcome Measures
Name Time Method Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria) 6 months
Trial Locations
- Locations (7)
Silesian Medical University
🇵🇱Katowice, Poland
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Charité University Hospital Berlin
🇩🇪Berlin, Germany
5th Medical Clinic, Clinic North
🇩🇪Nuremberg, Germany
University Hospital Hamburg Eppendorf
🇩🇪Hamburg, Germany
Karolinska University Hospital & Karolinska Institute
🇸🇪Stockholm, Sweden
University Hospital Rostock
🇩🇪Rostock, Germany