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Acute Graft-Versus-Host Disease (aGvHD) Prophylaxis With ATG-Fresenius in Matched Unrelated Donor-Stem Cell Transplantation (MUD-SCT)

Primary Purpose

Graft vs Host Disease

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
ATG-Fresenius S
Sponsored by
Neovii Biotech
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Graft vs Host Disease focused on measuring GvHD, aGvHD prophylaxis, Matched unrelated donor, ATG, SCT, BMT, polyclonal antibody, GvHD prophylaxis for patients with ALL, AML, CML, MDS, OMF, Patients with allogeneic BM or PBSC transplantation, Patients with a matched unrelated donor

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participation of patients in simultaneous diagnostic and comprehensive therapeutical trials for certain entities is allowed.

  • Patients 18-60 years of age;

  • Patients suffering from one of the following diseases:

    • AML: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure);
    • ALL: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure);
    • MDS, if transplantation is medically indicated: RA (with poor risk factors as classified by the International Prognostic Scoring System of MDS), RARS, RAEB, RAEB-t, CMML;
    • CML: beyond 1st chronic phase (CP1): accelerated phase, blast crisis, chronic phase (CP2, CP3);
    • OMF, if transplantation is medically indicated: Osteomyelofibrosis;
  • Patients designated to undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem cell transplantation;
  • Patients with a HLA-A, -B (DNA-based, 2 digits), HLA-DRB1, -DQB1 (DNA-based 4 digits) matched (8 out of 8 alleles) unrelated donor; serological typing is not required
  • Patients with a Karnofsky Performance Score (KPS): > 60%;
  • Patients who underwent all obligatory screening examinations (special examinations within the last 4 weeks);
  • Patients who have given their written informed consent to participate in the study.

Exclusion Criteria:

  • Patients with significant cardiac (e.g. ejection fraction <50%), pulmonary (e.g. FEV1 <50%), renal (e.g. creatinine > 1.5 mg/dl), metabolic (e.g. bilirubin > 2.0 mg/dl) and/or CNS disease, currently uncontrolled by treatment, which may interfere with the completion of the study;
  • Patients with any bacterial, viral, or fungal infections not under adequate antimicrobial control;
  • Patients who are known to have serum hepatitis or who are carriers of the Hepatitis B surface antigen (HBs-Ag), or Hepatitis C antibody, or who are known to have a positive result to the test of HIV antibodies;
  • Patients with any additional concurrent or previous malignant disease;
  • Patients with known hypersensitivity to rabbit immunoglobulin antibodies in past patient history or with known allergy to any substance chemically related to the study medication;
  • Pregnant (β-HCG test) or lactating women;
  • Patients who formerly underwent transplantation including previous autologous transplants;
  • Patients who cannot communicate reliably with the investigator or who are not likely to cope with the requirements of the study.

Sites / Locations

  • Universität Freiburg, Medizinische Klinik, Abteilung Innere Medizin I, Hämatologie/Onkologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

ATG-F

non-ATG-F

Arm Description

ATG-Fresenius S (20 mg/kg body weight at days -3 to -1 (total dose: 60 mg/kg) cyclosporine A (target trough level > 200ng/ml (day -1 until day +100) methotrexate: 15mg/m2 at day +1, 10mg/m2 at days +3, +6, and +11

cyclosporine A (target trough level > 200ng/ml (day -1 until day +100) methotrexate: 15mg/m2 at day +1, 10mg/m2 at days +3, +6, and +11

Outcomes

Primary Outcome Measures

Primary: Early treatment failure defined by the occurrence of severe acute GvHD (°III-°IV) or early mortality within 100 days post transplantation.

Secondary Outcome Measures

Time to onset of acute GvHD, incidence and severity of infections until day +100, time to engraftment, incidence of cGvHD, disease free survival, relapse, death without relapse, overall survival, safety, tolerability.

Full Information

First Posted
April 3, 2008
Last Updated
December 9, 2011
Sponsor
Neovii Biotech
Collaborators
University Medical Center Freiburg
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1. Study Identification

Unique Protocol Identification Number
NCT00655343
Brief Title
Acute Graft-Versus-Host Disease (aGvHD) Prophylaxis With ATG-Fresenius in Matched Unrelated Donor-Stem Cell Transplantation (MUD-SCT)
Official Title
GvHD Prophylaxis With ATG-Fresenius S in Allogeneic Stem Cell Transplantation From Matched Unrelated Donors: A Randomized Phase III Multicenter Trial Comparing a Standard GvHD Prophylaxis With Cyclosporine A and Methotrexate With Additional Pretransplant ATG-Fresenius S
Study Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
February 2003 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neovii Biotech
Collaborators
University Medical Center Freiburg

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study aim is to evaluate the influence of the anti-T-lymphocyte globulin ATG-Fresenius S given pre-transplant in addition to standard GvHD prophylaxis with cyclosporine A and a short course of methotrexate with respect to efficacy and safety.
Detailed Description
To assess the efficacy of ATG-FRESENIUS S in addition to standard therapy (cyclosporine A / methotrexate) with respect to early treatment failure defined by the occurrence of severe acute GvHD grade III-IV or early mortality within 100 days post transplantation compared to standard therapy alone. All patients receive myeloablative therapy. Recommended regimens: For patients with ALL: fractionated TBI (8-12 Gy) plus cyclophosphamide (1-2 x 60 mg/kg) [etoposide/melfalan are also allowed]. For all other indications: either TBI (8-12 Gy) or busulfan (per os 14-16 mg/kg b.w. or equivalent for IV administration) plus cyclophosphamide (1-2 x 60 mg/kg) or thiotepa ≥ 15 mg/kg or BCNU ≥ 300 mg/m2. Conditioning regimens may differ from centre to centre; each centre decides for constant (disease specific) regimen(s) throughout the whole study period. Standard GvHD prophylaxis consists of cyclosporine A (target trough level ≥ 200 ng/ml starting from day -1 until day +100) and short course methotrexate (15 mg/m2 at day +1, 10 mg/m2 at days +3, +6 and +11).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft vs Host Disease
Keywords
GvHD, aGvHD prophylaxis, Matched unrelated donor, ATG, SCT, BMT, polyclonal antibody, GvHD prophylaxis for patients with ALL, AML, CML, MDS, OMF, Patients with allogeneic BM or PBSC transplantation, Patients with a matched unrelated donor

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
202 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATG-F
Arm Type
Experimental
Arm Description
ATG-Fresenius S (20 mg/kg body weight at days -3 to -1 (total dose: 60 mg/kg) cyclosporine A (target trough level > 200ng/ml (day -1 until day +100) methotrexate: 15mg/m2 at day +1, 10mg/m2 at days +3, +6, and +11
Arm Title
non-ATG-F
Arm Type
No Intervention
Arm Description
cyclosporine A (target trough level > 200ng/ml (day -1 until day +100) methotrexate: 15mg/m2 at day +1, 10mg/m2 at days +3, +6, and +11
Intervention Type
Drug
Intervention Name(s)
ATG-Fresenius S
Other Intervention Name(s)
ATG-Fresenius, Anti-T-Lymphocyte globulin
Intervention Description
20 mg rabbit immunoglobulin (IgG) in 1 ml of sterile solution 20 mg/kg body weight per day diluted in 500 ml physiological saline, slow intravenous infusion at days -3, -2, -1 prior to transplantation
Primary Outcome Measure Information:
Title
Primary: Early treatment failure defined by the occurrence of severe acute GvHD (°III-°IV) or early mortality within 100 days post transplantation.
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Time to onset of acute GvHD, incidence and severity of infections until day +100, time to engraftment, incidence of cGvHD, disease free survival, relapse, death without relapse, overall survival, safety, tolerability.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participation of patients in simultaneous diagnostic and comprehensive therapeutical trials for certain entities is allowed. Patients 18-60 years of age; Patients suffering from one of the following diseases: AML: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure); ALL: 1st complete remission (CR1) or beyond 1st remission (CR2, CR3), in relapse, not in remission (primary refractory, induction failure); MDS, if transplantation is medically indicated: RA (with poor risk factors as classified by the International Prognostic Scoring System of MDS), RARS, RAEB, RAEB-t, CMML; CML: beyond 1st chronic phase (CP1): accelerated phase, blast crisis, chronic phase (CP2, CP3); OMF, if transplantation is medically indicated: Osteomyelofibrosis; Patients designated to undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem cell transplantation; Patients with a HLA-A, -B (DNA-based, 2 digits), HLA-DRB1, -DQB1 (DNA-based 4 digits) matched (8 out of 8 alleles) unrelated donor; serological typing is not required Patients with a Karnofsky Performance Score (KPS): > 60%; Patients who underwent all obligatory screening examinations (special examinations within the last 4 weeks); Patients who have given their written informed consent to participate in the study. Exclusion Criteria: Patients with significant cardiac (e.g. ejection fraction <50%), pulmonary (e.g. FEV1 <50%), renal (e.g. creatinine > 1.5 mg/dl), metabolic (e.g. bilirubin > 2.0 mg/dl) and/or CNS disease, currently uncontrolled by treatment, which may interfere with the completion of the study; Patients with any bacterial, viral, or fungal infections not under adequate antimicrobial control; Patients who are known to have serum hepatitis or who are carriers of the Hepatitis B surface antigen (HBs-Ag), or Hepatitis C antibody, or who are known to have a positive result to the test of HIV antibodies; Patients with any additional concurrent or previous malignant disease; Patients with known hypersensitivity to rabbit immunoglobulin antibodies in past patient history or with known allergy to any substance chemically related to the study medication; Pregnant (β-HCG test) or lactating women; Patients who formerly underwent transplantation including previous autologous transplants; Patients who cannot communicate reliably with the investigator or who are not likely to cope with the requirements of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juergen Finke, Prof. Dr.
Organizational Affiliation
Albert-Ludwigs-University Freiburg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universität Freiburg, Medizinische Klinik, Abteilung Innere Medizin I, Hämatologie/Onkologie
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79110
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
21467544
Citation
Socie G, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhauser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Finke J; ATG-Fresenius Trial Group. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011 Jun 9;117(23):6375-82. doi: 10.1182/blood-2011-01-329821. Epub 2011 Apr 5.
Results Reference
result
PubMed Identifier
19695955
Citation
Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhauser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socie G; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009 Sep;10(9):855-64. doi: 10.1016/S1470-2045(09)70225-6. Epub 2009 Aug 18.
Results Reference
result
PubMed Identifier
28583289
Citation
Finke J, Schmoor C, Bethge WA, Ottinger H, Stelljes M, Volin L, Heim D, Bertz H, Grishina O, Socie G. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. Lancet Haematol. 2017 Jun;4(6):e293-e301. doi: 10.1016/S2352-3026(17)30081-9.
Results Reference
derived

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Acute Graft-Versus-Host Disease (aGvHD) Prophylaxis With ATG-Fresenius in Matched Unrelated Donor-Stem Cell Transplantation (MUD-SCT)

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