Dose-range Finding Treosulfan-based Conditioning

• Status: Completed
• Trial end date: 2006-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: medac GmbH
• Treatments: Busulfan; Treosulfan

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