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

Sponsors and Collaborators:	Fresenius Biotech GmbH Zentrum Klinische Studien/Center for Clinical Trials (ZKS/CCT)
Information provided by:	Fresenius Biotech GmbH
ClinicalTrials.gov Identifier:	NCT00655343

Purpose

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.

Condition	Intervention	Phase
Graft vs Host Disease	Drug: ATG-Fresenius S	Phase III

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Fresenius Biotech GmbH:

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. [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

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. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Enrollment:	202
Study Start Date:	February 2003
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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	Drug: ATG-Fresenius S 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
2: No Intervention 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

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).

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00655343

Locations

Germany, Baden-Württemberg
Universität Freiburg, Medizinische Klinik, Abteilung Innere Medizin I, Hämatologie/Onkologie
Freiburg, Baden-Württemberg, Germany, 79110

Sponsors and Collaborators

Fresenius Biotech GmbH

Zentrum Klinische Studien/Center for Clinical Trials (ZKS/CCT)

Investigators

Principal Investigator:

Juergen Finke, Prof. Dr.

Albert-Ludwigs-University Freiburg

More Information

No publications provided

Study ID Numbers:	AP-AS-21-DE
Study First Received:	April 3, 2008
Last Updated:	April 8, 2008
ClinicalTrials.gov Identifier:	NCT00655343 History of Changes
Health Authority:	Germany: Paul-Ehrlich-Institut

Keywords provided by Fresenius Biotech GmbH:

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

Study placed in the following topic categories:

Graft Versus Host Disease
Antibodies
Cyclosporine
Methotrexate

Graft vs Host Disease
Cyclosporins
Homologous Wasting Disease
Immunoglobulins

Additional relevant MeSH terms:

Immune System Diseases
Graft vs Host Disease

ClinicalTrials.gov processed this record on May 07, 2009