Clinical trial NCT01063647: Dose-range Finding Treosulfan-based Conditioning
Official title: Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematological Malignancies
Keywords: Treosulfan
Allogeneic stem cell transplantation
Conditioning therapy
Lead sponsor: medac GmbH
Sponsor class: INDUSTRY
First posted: 2010-02-05
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria)
timeFrame: 6 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Berlin
country: Germany
facility: Charité University Hospital Berlin
city: Hamburg
country: Germany
facility: University Hospital Hamburg Eppendorf
city: Nuremberg
country: Germany
facility: 5th Medical Clinic, Clinic North
city: Rostock
country: Germany
facility: University Hospital Rostock
city: Katowice
country: Poland
facility: Silesian Medical University
city: Stockholm
country: Sweden
facility: Karolinska University Hospital & Karolinska Institute
Study officials:
affiliation: University Hospital Rostock
name: Mathias Freund, MD
role: PRINCIPAL_INVESTIGATOR
References: