Clinical trial NCT01332006: Intra-bone Cord Blood Transplantation
Official title: Intra-bone Cord Blood Transplantation for Hematological Malignancies Lacking a HLA Suitable Donor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hematologic Neoplasms
Lead sponsor: Università degli Studi di Brescia
Sponsor class: OTHER
First posted: 2011-04-08
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: For the great majority of hematological malignancies, hemopoietic stem cell (HSC) transplant is the only possible cure. The source of HSC is usually bone marrow (BM) or peripheral blood cell (PBSC) mobilized by granulocyte growth factor. Transplant needs a HLA compatible donor weather related or unrelated. A suitable compatible donor can be found in at least 70% of the patients. Thus, at least 30% of patients with indication for allogeneic HSC transplant are not able to undergo the procedure because of the lack of a HLA compatible donor. Cord blood (CB) cells represent another possible source, that needs a lower degree of HLA compatibility. CB transplant, however, offers a lower number of HSC. Thus, adult patient rarely may benefit from this source of stem cells, mainly beacuse thie body weight is too high to have ad adequate number of cell per kg. Recently, experimental animal models confirmed that an adequate recovery of allogeneic hemopoiesis can be achieved via intrabone injection, using a 1Log lower number of cells compared to the intravenous way (Yahata 2003, Castello 2004). Safety and feasibility of intrabone infusion was verified by two clinical studies on humans: the first was conducted by Ringden O. et al. in 18 patients using BM as a source of SC. No side effects and complete engraftment of donor hemopoiesis was observed; the second one was conducted by Frassoni et al. (Frassoni 2008) with CB as the source of HSC.

The aim of this study is to evaluate the intrabone infusion of compatible CB in patients with haematological malignancies lacking a HLA matched donor.

We will perform:

evaluation of the engraftment kinetics; evaluation of the chimerism degree at 30, 60, 100 days, 6 months and 1 year after transplant; studies on immunological reconstitution and the role of the NK compartment.


Eligibility criteria: Inclusion Criteria:

* Age between 18 and 65 years.
* Patients affected by hematological malignancies without a HLA identical sibling donor or unrelated donor.
* Informed consent.

Exclusion Criteria:

* Patients with ECOG \< 2.
* Patients with blood creatine \> 2 mg/dl or with transaminase or cholestase index \> 5 times compared to normality upper limits.
* Patients with Cardiac Fraction Ejection \< 40%.
* Patients with DLCO \< 60% or Diffusing Lung Capacity of carbon monoxide attesting a severe pulmonary insufficiency.
* Patients with peripheral blast cell count over 10%.
* Second neoplasia diagnosed no more than 2 years before.
* Patients with active or suspected infection by fungi for which a therapeutic treatment is ongoing.
* HIV positive patients.
* HCV-RNA and HBV-DNA positive patients
* Pregnant or lactating women.
* Severe mental diseases.

Primary outcomes:
measure: Proportion of transplanted patients with successful engraftment at day +30
timeFrame: 30 days post transplantation
Secondary outcomes:
measure: Clinical response with the analysis of global survival, survival without relapse, relapse incidence
timeFrame: 3 years from transplantation
measure: Infections' Incidence
timeFrame: One year after transplantation
measure: Chimerism monitoring on selected cell populations
timeFrame: Every three months and until one year after transplantation
measure: Immunological reconstitution
timeFrame: One year after transplantation
measure: Acute an Chronic GVHD
timeFrame: One year after transplantation
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: USD TMO Adulti, Piazzale Spedali Civili
Study officials:
affiliation: USD TMO Adulti
name: Domenico Russo, Full Professor
role: PRINCIPAL_INVESTIGATOR
References: