Dose-range Finding Treosulfan-based Conditioning

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01063647
Recruitment Status : Completed
First Posted : February 5, 2010
Last Update Posted : February 5, 2010
Information provided by:
medac GmbH

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.

Condition or disease Intervention/treatment Phase
Hematological Malignancies Drug: Treosulfan Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study
Study Start Date : November 2001
Actual Primary Completion Date : June 2005
Actual Study Completion Date : June 2006

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 Name: Ovastat
Experimental: 2
Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4)
Drug: Treosulfan
12 g/m² i.v. infusion, day -6, -5, -4
Other Name: Ovastat
Experimental: 3
Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)
Drug: Treosulfan
14 g/m² i.v. infusion, day -6, -5, -4
Other Name: Ovastat

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria) [ Time Frame: 6 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01063647

Helsinki University Central Hospital
Helsinki, Finland, FIN-00290
Charité University Hospital Berlin
Berlin, Germany, 12203
University Hospital Hamburg Eppendorf
Hamburg, Germany, 20246
5th Medical Clinic, Clinic North
Nuremberg, Germany, 90340
University Hospital Rostock
Rostock, Germany, 18057
Silesian Medical University
Katowice, Poland, 40-029
Karolinska University Hospital & Karolinska Institute
Stockholm, Sweden, 141 86
Sponsors and Collaborators
medac GmbH
Principal Investigator: Mathias Freund, MD University Hospital Rostock

Responsible Party: Joachim Baumgart, PhD, medac GmbH Identifier: NCT01063647     History of Changes
Other Study ID Numbers: MC-FludT.6/L
First Posted: February 5, 2010    Key Record Dates
Last Update Posted: February 5, 2010
Last Verified: February 2010

Keywords provided by medac GmbH:
Allogeneic stem cell transplantation
Conditioning therapy

Additional relevant MeSH terms:
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Myeloablative Agonists