Clinical trial NCT01810926: T&B Depletion Non Malignant
Official title: A Phase II Multicentre, Randomized, Controlled Open-label Study on the Use of Anti-thymocyte Globulin and Rituximab for Immunomodulation of Graft-versus-host Disease in Allogeneic Matched Transplants for Non Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Graft Versus Host Disease
Keywords: indication for HSCT
matched related donor
MRD
Matched Unrelated Donor
MUD
Lead sponsor: Bambino Gesù Hospital and Research Institute
Sponsor class: OTHER
Collaborators: name: University of Milano Bicocca
name: medac GmbH
name: Fresenius AG
First posted: 2013-03-14
Enrollment: 130
Sex: ALL
Minimum age (years): 28
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: • The primary aim of the present trial is to assess in a randomized fashion the benefit on standard graft-versus-host disease (GVHD) prophylaxis of the addition of ATG-Fresenius S ® in transplants from matched related donors (MRD) and of anti-CD20 rituximab in transplants from matched unrelated donors (MUD). Both safety and efficacy of the treatment will be assessed, in particular in respect to the clinical status of the patient, i.e. prevention of graft failure and chronic GvHD and of Ebstein Barr virus (EBV) viremia for MUD patients.

The conditioning proposed combines myeloablative drugs with a favorable safety profile such as treosulfan, thiotepa (Tepadina®) and fludarabine with the intent to reduce the traditional immediate and late toxicity of busulfan and cyclophosphamide.

Detailed description: For patients transplanted from a MRD

The primary end-point is the cumulative incidence of a combined end-point defined as the time from randomization to:

* primary and secondary graft failure,
* aGVHD II-IV,
* cGVHD,
* death, whichever occurs first.

For patients transplanted from a MUD

The primary end-point is the cumulative incidence of a combined end-point defined as the time from randomization to:

* aGVHD II-IV,
* EBV viremia, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

* non malignant haematological and inherited metabolic disorders benefiting from an allogeneic HSCT conditioned with a myeloablative regimen
* Availability of a matched related donor (MRD) or Matched Unrelated Donor (MUD)
* Lansky or Karnofsky Index ≥ 60
* Inherited metabolic disorders: DQ ≥ 70 (+ MRI Loes score ≤ 9 for adrenoleukodystrophy)
* Adequate cardiac, renal, hepatic and pulmonary functions as evidenced by:
* Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
* Heart shortening fraction (left-ventricle) \> 28 % or LVEF \> 55%
* Serum bilirubin ≤ 1.5 × ULN (except for Wolman disease),
* AST and ALT ≤ 2.5 × ULN (except for thalassemic syndromes and Wolman disease)
* Pulmonary function: if cooperative: FEV1 and FVC on pulmonary function testing \> 60 %; if non cooperative: pulse oximetry \> 95 % in room air
* Availability of autologous back up marrow (\> 2 x 108 TNC+ cells/kg or \> 2 x 106 CD34+ cells/kg) for MUD
* Adequate contraception in female patients of child-bearing potential
* Signed informed consent

Exclusion Criteria:

* Any malignancy
* Liver cirrhosis evidenced on liver histology (performed in suspicious cases or in case of Wolman disease)
* HIV- positivity
* Clinically significant pleural effusion or ascites
* Pregnancy or lactation
* Known hypersensitivity to trial drugs
* Participation in another experimental drug trial in the 2 months preceding enrollment
* Non-cooperative behaviour or non-compliance
* Previous HSCT

Primary outcomes:
measure: Acute graft-versus-host disease (aGVHD) II-IV and chronic GvHD
timeFrame: From date of randomization assessed up to 100 months
Secondary outcomes:
measure: Chronic graft-versus-host disease (cGVHD)
timeFrame: From date of randomization assessed up to 100 months
measure: Treatment related mortality (TRM)
timeFrame: From date of randomization assessed up to 100 months
measure: Overall survival (OS)
timeFrame: From date of randomization assessed up to 100 months
Other outcomes:
Locations:
city: Cagliari
country: Italy
facility: University of Cagliari
city: Milano
country: Italy
facility: San Raffaele Scientific Institute
city: Monza
country: Italy
facility: University of Milano-Bicocca San Gerardo Hospital
city: Rome
country: Italy
facility: Bambino Gesù Hospital and Research Institute
Study officials:
affiliation: Bambino Gesù Hospital and Research Institute
name: Franco Locatelli, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Sacchi N, van Lint MT, Bosi A; Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006 May;12(5):560-5. doi: 10.1016/j.bbmt.2005.12.034.
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