Acute Graft-Versus-Host Disease (aGvHD) Prophylaxis With ATG-Fresenius in Matched Unrelated Donor-Stem Cell Transplantation (MUD-SCT)
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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 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention |
| 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 |
- 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 ]
- 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 |
| Study Completion Date: | March 2009 |
| Primary Completion Date: | March 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: ATG-F
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 Other Names:
|
|
No Intervention: non-ATG-F
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 |
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| Germany | |
| Universität Freiburg, Medizinische Klinik, Abteilung Innere Medizin I, Hämatologie/Onkologie | |
| Freiburg, Baden-Württemberg, Germany, 79110 | |
| Principal Investigator: | Juergen Finke, Prof. Dr. | Albert-Ludwigs-University Freiburg |
More Information
Publications:
| Responsible Party: | Fresenius Biotech GmbH |
| ClinicalTrials.gov Identifier: | NCT00655343 History of Changes |
| Other Study ID Numbers: | AP-AS-21-DE |
| Study First Received: | April 3, 2008 |
| Last Updated: | December 9, 2011 |
| 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 |
Additional relevant MeSH terms:
|
Graft vs Host Disease Immune System Diseases Cyclosporins Cyclosporine Methotrexate Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antifungal Agents |
Anti-Infective Agents Therapeutic Uses Dermatologic Agents Antirheumatic Agents Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Antimetabolites, Antineoplastic Antimetabolites Antineoplastic Agents Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013