Dose-range Finding Treosulfan-based Conditioning

November 2, 2023 updated by: medac GmbH

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

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: 6 months
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)
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

medac GmbH

Investigators

  • Principal Investigator: Mathias Freund, MD, University Hospital Rostock

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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 (Estimated)

November 3, 2023

Last Update Submitted That Met QC Criteria

November 2, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC-FludT.6/L

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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