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

NCT00655343 | Completed Phase 3 DMC

• 1 other identifier: AP-AS-21-DE
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  100 days

Secondary Outcomes (1)

• 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.

  24 months

Study Arms (2)

ATG-F

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

non-ATG-F

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

Interventions

ATG-Fresenius S DRUG

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

Also known as: ATG-Fresenius, Anti-T-Lymphocyte globulin

ATG-F

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neovii Biotech: lead
• University Medical Center Freiburg: collaborator

Study Sites (1)

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

Freiburg im Breisgau, Baden-Wurttemberg, 79110, Germany

Location

Related Publications (4)

• 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.

  PMID: 21467544 RESULT

• 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.

  PMID: 19695955 RESULT

• Chakupurakal G, Freudenberger P, Skoetz N, Ahr H, Theurich S. Polyclonal anti-thymocyte globulins for the prophylaxis of graft-versus-host disease after allogeneic stem cell or bone marrow transplantation in adults. Cochrane Database Syst Rev. 2023 Jun 21;6(6):CD009159. doi: 10.1002/14651858.CD009159.pub3.

  PMID: 37341189 DERIVED

• 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.

  PMID: 28583289 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Immune System Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Juergen Finke, Prof. Dr.

  Albert-Ludwigs-University Freiburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2008
• First Posted: April 9, 2008
• Study Start: February 1, 2003
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2009
• Last Updated: December 12, 2011

Record last verified: 2011-12

Locations

DE (1)