Hematological Malignancies
Conditions
Keywords
Treosulfan, Allogeneic stem cell transplantation, Conditioning therapy
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.
Interventions
DRUGTreosulfan
10 g/m² i.v. infusion, day -6, -5, -4
Sponsors
medac GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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) 2. 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. 3. Age \> 18 years 4. Karnofsky Index \> 80 % 5. Adequate contraception in female patients of child-bearing potential 6. Co-operative behavior of individual patients 7. Written informed consent
Exclusion criteria
1. Completely chemotherapy-resistant disease 2. Severe cardiac insufficiency, severe cardio-vascular or other severe concomitant diseases 3. Symptomatic malignant involvement of the CNS 4. Active infectious disease 5. HIV-positive or active hepatitis infection 6. Impaired liver function (Bilirubin \> 1.5 x upper normal limit; Transaminases \> 3.0 x upper normal limit) 7. Impaired renal function (Creatinine-clearance \< 60 ml/min; Serum Creatinine \> 1.5 x upper normal limit). 8. Pleural effusion or ascites \> 1.0 L 9. Pregnancy or lactation 10. Known hypersensitivity to fludarabine and/or treosulfan 11. Parallel participation in another experimental drug trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria) | 6 months |
Countries
Finland, Germany, Poland, Sweden
Contacts
PRINCIPAL_INVESTIGATORMathias Freund, MD
University Hospital Rostock
Outcome results
None listed