Dose-range Finding Treosulfan-based Conditioning

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

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.

Study Overview

• Status: Completed
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Treosulfan; Drug: Treosulfan; Drug: Treosulfan

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, FIN-00290
    • Helsinki University Central Hospital
• Germany
  • Berlin, Germany, 12203
    • Charité University Hospital Berlin
  • Hamburg, Germany, 20246
    • University Hospital Hamburg Eppendorf
  • Nuremberg, Germany, 90340
    • 5th Medical Clinic, Clinic North
  • Rostock, Germany, 18057
    • University Hospital Rostock
• Poland
  • Katowice, Poland, 40-029
    • Silesian Medical University
• Sweden
  • Stockholm, Sweden, 141 86
    • Karolinska University Hospital & Karolinska Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4)	Drug: Treosulfan; 10 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat; Drug: Treosulfan; 12 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat; Drug: Treosulfan; 14 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat
Experimental: 2; Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4)	Drug: Treosulfan; 10 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat; Drug: Treosulfan; 12 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat; Drug: Treosulfan; 14 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat
Experimental: 3; Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)	Drug: Treosulfan; 10 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat; Drug: Treosulfan; 12 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat; Drug: Treosulfan; 14 g/m² i.v. infusion, day -6, -5, -4; Other Names: Ovastat

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: medac GmbH
• Investigators: Principal Investigator: Mathias Freund, MD, University Hospital Rostock

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (Actual): June 1, 2005
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: February 3, 2010
• First Submitted That Met QC Criteria: February 4, 2010
• First Posted (Estimated): February 5, 2010

Study Record Updates

• Last Update Posted (Actual): August 12, 2026
• Last Update Submitted That Met QC Criteria: August 10, 2026
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Treosulfan; Allogeneic stem cell transplantation; Conditioning therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; treosulfan
• Other Study ID Numbers: MC-FludT.6/L