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Dose-range Finding Treosulfan-based Conditioning

Primary Purpose

Hematological Malignancies

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Treosulfan
Treosulfan
Treosulfan
Sponsored by
medac GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematological Malignancies focused on measuring Treosulfan, Allogeneic stem cell transplantation, Conditioning therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Helsinki University Central Hospital
  • Charité University Hospital Berlin
  • University Hospital Hamburg Eppendorf
  • 5th Medical Clinic, Clinic North
  • University Hospital Rostock
  • Silesian Medical University
  • Karolinska University Hospital & Karolinska Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

1

2

3

Arm Description

Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4)

Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4)

Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria)

Full Information

First Posted
February 3, 2010
Last Updated
February 4, 2010
Sponsor
medac GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT01063647
Brief Title
Dose-range Finding Treosulfan-based Conditioning
Official Title
Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2010
Overall Recruitment Status
Completed
Study Start Date
November 2001 (undefined)
Primary Completion Date
June 2005 (Actual)
Study Completion Date
June 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
medac GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Malignancies
Keywords
Treosulfan, Allogeneic stem cell transplantation, Conditioning therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4)
Arm Title
2
Arm Type
Experimental
Arm Description
Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4)
Arm Title
3
Arm Type
Experimental
Arm Description
Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)
Intervention Type
Drug
Intervention Name(s)
Treosulfan
Other Intervention Name(s)
Ovastat
Intervention Description
10 g/m² i.v. infusion, day -6, -5, -4
Intervention Type
Drug
Intervention Name(s)
Treosulfan
Other Intervention Name(s)
Ovastat
Intervention Description
12 g/m² i.v. infusion, day -6, -5, -4
Intervention Type
Drug
Intervention Name(s)
Treosulfan
Other Intervention Name(s)
Ovastat
Intervention Description
14 g/m² i.v. infusion, day -6, -5, -4
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria)
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) 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. Age > 18 years Karnofsky Index > 80 % Adequate contraception in female patients of child-bearing potential Co-operative behavior of individual patients Written informed consent Exclusion Criteria: Completely chemotherapy-resistant disease Severe cardiac insufficiency, severe cardio-vascular or other severe concomitant diseases Symptomatic malignant involvement of the CNS Active infectious disease HIV-positive or active hepatitis infection Impaired liver function (Bilirubin > 1.5 x upper normal limit; Transaminases > 3.0 x upper normal limit) Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit). Pleural effusion or ascites > 1.0 L Pregnancy or lactation Known hypersensitivity to fludarabine and/or treosulfan Parallel participation in another experimental drug trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mathias Freund, MD
Organizational Affiliation
University Hospital Rostock
Official's Role
Principal Investigator
Facility Information:
Facility Name
Helsinki University Central Hospital
City
Helsinki
ZIP/Postal Code
FIN-00290
Country
Finland
Facility Name
Charité University Hospital Berlin
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
University Hospital Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
5th Medical Clinic, Clinic North
City
Nuremberg
ZIP/Postal Code
90340
Country
Germany
Facility Name
University Hospital Rostock
City
Rostock
ZIP/Postal Code
18057
Country
Germany
Facility Name
Silesian Medical University
City
Katowice
ZIP/Postal Code
40-029
Country
Poland
Facility Name
Karolinska University Hospital & Karolinska Institute
City
Stockholm
ZIP/Postal Code
141 86
Country
Sweden

12. IPD Sharing Statement

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Dose-range Finding Treosulfan-based Conditioning

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