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

Sponsor

Neovii Biotech (Industry)

Overall Status

Completed

CT.gov ID

NCT00655343

Collaborator

University Medical Center Freiburg (Other)

202

Enrollment

Location

Arms

72.9

Duration (Months)

2.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Graft vs Host Disease	Drug: ATG-Fresenius S	Phase 3

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Feb 1, 2003

Actual Primary Completion Date :

Mar 1, 2007

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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: ATG-Fresenius Anti-T-Lymphocyte globulin
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

Arm

Intervention/Treatment

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:

ATG-Fresenius

Anti-T-Lymphocyte globulin

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

Outcome Measures

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. [100 days]

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. [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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.