Dose-range Finding Treosulfan-based Conditioning

Hematological Malignancies Clinical Trial

Official title:

Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01063647
• Other study ID #: MC-FludT.6/L
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2001
• Est. completion date: June 2006

Study information

• Verified date: November 2023
• Source: medac GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: June 2006
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Drug:
• Treosulfan
10 g/m² i.v. infusion, day -6, -5, -4
• Treosulfan
12 g/m² i.v. infusion, day -6, -5, -4
• Treosulfan
14 g/m² i.v. infusion, day -6, -5, -4

Locations

Country	Name	City	State
Finland	Helsinki University Central Hospital	Helsinki
Germany	Charité University Hospital Berlin	Berlin
Germany	University Hospital Hamburg Eppendorf	Hamburg
Germany	5th Medical Clinic, Clinic North	Nuremberg
Germany	University Hospital Rostock	Rostock
Poland	Silesian Medical University	Katowice
Sweden	Karolinska University Hospital & Karolinska Institute	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
medac GmbH

Countries where clinical trial is conducted

Finland,  Germany,  Poland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria)		6 months