Intrabone Infusion of Cord Blood in Adults With Hematological Malignancies (IBCB)

March 18, 2021 updated by: Francesca Bonifazi, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Intrabone Infusion of Cord Blood Hemopoietic Stem Cells in Adult Patients With High Risk Haematological Malignancies.

The purpose of this study is to evaluate the engraftment of donor hemopoiesis (proportion of transplanted patients with successful engraftment at day +42) in adult patients affected by high risk hematological malignancies after intrabone infusion of cord blood.

Study Overview

Status

Completed

Detailed Description

For many hematological malignancies, hemopoietic stem cell (HSC) transplant is the only possible treatment. The source of HSC is often bone marrow (BM) or, in the past 10 years, peripheral blood cell (PBSC) mobilized by granulocyte growth factor. Transplant needs a HLA compatible (related or unrelated) donor. Around 10-30% 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, which needs a lower degree of HLA compatibility, this type of transplant, however, offers a lower number of HSC. For this reason, adult patients, until now, could not use this source, because of the not suitable number of cell per kg, of recipient body weight. Recently, in experimental animal models it was observed that intrabone HSC transplant allows, in the recipient, engraftment of donor hemopoiesis by using a 1Log (10-1) 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 without any evidence of collateral effects and with complete engraftment of donor hemopoiesis with BM as a source of HSC (Hagglund 1998); 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 instead of the intravenous one, for the HSC transplant from CB in patients with haematological malignancies when it is not possible to find 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.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bologna, Italy, 40138
        • Hematology Institute "L. and A. Seràgnoli", S. Orsola-Malpighi University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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-RNA positive patients (it is possible to enrol them after discussion with the Principal Investigator).
  • Pregnant or lactating women.
  • Severe mental diseases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intrabone cord blood infusion
All adults patients with hematological malignancies, lacking a HLA matched donor but with a HLA compatible CB unit, fulfilling the inclusion criteria, will undergo to intrabone HSC infusion of CB.

Myeloablative conditioning regimen (MAC):

i.v. Busulfan 12.8 mg/kg, Cyclophosphamide 120 mg/kg, ATG-Fresenius 30 mg/kg

Reduced intensity conditioning regimen (RIC):

Tiothepa 10 mg/kg, Fludarabine 100 mg/kg, Cyclophosphamide 100 mg/kg, ATG-Fresenius 30 mg/kg

GVHD prophylaxis:

Cyclosporine 1 mg/kg since day -7 to +120, Mycophenolate 15 mg kg x 2 since day +1 to +27

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of transplanted patients with successful engraftment at day +42
Time Frame: Within the first 42 days
Within the first 42 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Clinical response with the analysis of global survival, survival without relapse, relapse incidence
Time Frame: 1 year
1 year
Acute and chronic GVHD incidence
Time Frame: For acute GVHD 100 days; for chronic GVHD 1 year
For acute GVHD 100 days; for chronic GVHD 1 year
Infection incidence
Time Frame: 1 year
1 year
Chimerism study on selected populations (myeloid, lymphoid, NK)
Time Frame: 30, 60, 100 days, 6 months and 1 year
30, 60, 100 days, 6 months and 1 year
Studies on immunological reconstitution
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Francesca Bonifazi, MD, S. Orsola-Malpighi University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

April 22, 2009

First Submitted That Met QC Criteria

April 22, 2009

First Posted (Estimate)

April 23, 2009

Study Record Updates

Last Update Posted (Actual)

March 19, 2021

Last Update Submitted That Met QC Criteria

March 18, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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