Graft vs Host Disease
Conditions
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
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).
Interventions
DRUGATG-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
Sponsors
University Medical Center Freiburg
Neovii Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
Germany
Outcome results
None listed