Early therapy of acute bone marrow rejection according to specific proteins detected in urine after bone marrow transplantation.

Active, not recruiting

• Conditions: Pre-emptive therapy of acute graft versus host disease with prednisolone according to specific proteomic patterns after allogeneic hematopoietic stem cell transplantation.; MedDRA version: 16.1Level: LLTClassification code 10018652Term: Graft versus host reactionSystem Organ Class: 100000004870; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2008-005862-30-DE
• Lead Sponsor: Medizinische Hochschule Hannover

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-15
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Written informed consent
• All patients = 18 years on day +7 (+/- 3) after 1st allo-HSCT
• Patients transplanted for: acute myeloid or lymphoid leukemia in CR (<5% leukemic blast cells in the bone marrow) or PR (<20% leukemic blast cells in the bone marrow); myelodysplastic and/or myeloproliferative syndromes: untreated, CR, PR; lymphomas: PR; chronic myeloid leukemia: CP; chronic lymphatic leukemia: CR, PR; multiple myeloma: CR, PR; severe aplastic anemia at the time of allogeneic HSCT
• aGvHD prophylaxis with any combination of the following: e.g. cyclosporin A (CsA), methotrexate (MTX), mycophenolic acid (MMF), tacrolimus, sirolimus, everolimus and others with or with-out immunosuppressive antibodies (e.g. anti-thymocyte globulin (ATG))
• Woman of childbearing potential must have a negative pregnancy test prior to HSCT
• Sufficient contraceptive methods for men and women of reproductive age at the beginning of the study and during the study and consent of the patient to used a sufficient contraceptive method within 6 months after the end of the study. Permitted double contraceptive methods are implants, injection preparation, intrauterine devices, portal cap, sterilization, hysterectomy, condoms, spermicide, vasectomy and/or sexual abstinence.

Prior to randomization:
• Positivity of aGvHD-specific proteomic pattern

(Patients enrolled, who can not be randomized, will be followed-up in the observational group).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 234
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion Criteria

• Patients after = 2nd allo-HSCT
• Patients transplanted in relapse of their underlying disease (AML, ALL: =20% leukemic blast cells in the bone marrow)
• Transplantation with CD34+-enriched or ex vivo T-cell-depleted stem cells, transplantation from syngeneic or haploidentical or cord blood donors
• Steroids as part of the acute GvHD prophylaxis
• Pregnant or nursing women
• Participation in an other therapeutic study within 30 days before and during this study

Prior to randomization:
• Patients with acute GvHD grade II to IV
• Acute renal failure (= 2x upper normal boundary of serum creatinine)
• Serious, life-threatening infection at the time of sampling for aGvHD proteomic pattern
• Relapse or progression of underlying disease

(Patients enrolled, who cannot be randomized, will be followed-up in the observational group).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To test the efficacy of pre-emptive immunosuppressive treatment (2-2.5mg prednisolone/kg BW/day) versus placebo immediately when a positive acute Graft-versus-Host disease (aGvHD,grade II-IV) and a specific proteomic pattern is observed. ;Secondary Objective: To test the efficacy of pre-emptive treatment of (1) severity of aGvHD, (2) allogeneic HSCT related mortality due to toxicitiy or infections, (3) overall survival, (4) incidence of leukemic relapses and (5) safety of pre-emptive treatment;Primary end point(s): Primary study endpoint:<br>Occurrence of aGvHD (= grade II) between time of randomization and 100 days after allo-HSCT. Death occurring between randomization and 100 days post allo-HSCT without aGvHD (= grade II) will be considered as treatment failure, equivalent to an aGvHD (= grade II) development.<br><br><br><br>;Timepoint(s) of evaluation of this end point: 100 days after allo-HSCT

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: (1) until 100 days after allo-HSCT<br>(2)-(6) until end of follow-up period (100 days + 365 days);Secondary end point(s): Secondary study endpoints:<br>(1) Severity of aGvHD until day 100 after allo-HSCT, (2) all aGvHD (= grade II), (3) severity of all aGvHD, (4) transplant-related mortality (TRM), (5) overall survival, (6) occurrence of leukemic relapses and (7) infectious complications.<br><br>Additional scientific endpoints: <br>To establish proteomic patterns specific for steroid-resistant aGvHD.