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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00886522
Recruitment Status : Completed
First Posted : April 23, 2009
Last Update Posted : April 15, 2016
Information provided by (Responsible Party):
Francesca Bonifazi, MD, St. Orsola Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hematological Malignancies Procedure: Intrabone cord blood infusion Phase 2

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  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intrabone Infusion of Cord Blood Hemopoietic Stem Cells in Adult Patients With High Risk Haematological Malignancies.
Study Start Date : April 2009
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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.
Procedure: Intrabone cord blood infusion

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

Primary Outcome Measures :
  1. Proportion of transplanted patients with successful engraftment at day +42 [ Time Frame: Within the first 42 days ]

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

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00886522

Hematology Institute "L. and A. Seràgnoli", S. Orsola-Malpighi University Hospital
Bologna, Italy, 40138
Sponsors and Collaborators
St. Orsola Hospital
Principal Investigator: Francesca Bonifazi, MD S. Orsola-Malpighi University Hospital

Additional Information:
Dick JE and Lapidot T. Stem cells take a shortcut to the bone marrow. Blood 2003(101):2901-2902.
Frassoni F, Gualandi F, Podestà M et al. Direct intra-bone injection of unrelated cord blood cells overcomes the problem of delayed/failure to engraft and improves the feasibility of haematopoietic transplant in adult patients. Bone Marrow Transp 41(81):21, 2008.
Hansen JA and Dupont B. HLA 2004 Immunobiology of the Human MHC. Proceedings of the 13th IHWC. IHWG Press 2004, Seattle, WA (USA).
Josefson A. A new method of treatment - intraossal injections. Acta Med Scand 1934; 81:550-564.
Rubinstein P, Carrier C, Carpenter C et al. Graft selection in unrelated placental/umbilical cord blood (PCB) transplantation: influence and weight of HLA match and cell dose on engraftment and survival [abstract]. Blood 2000; 96:588a.

Responsible Party: Francesca Bonifazi, MD, MD, St. Orsola Hospital Identifier: NCT00886522     History of Changes
Other Study ID Numbers: 152/2008/U/Sper
First Posted: April 23, 2009    Key Record Dates
Last Update Posted: April 15, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Francesca Bonifazi, MD, St. Orsola Hospital:
Anti-thymocyte globulin Fresenius
Cord blood
Human Leucocyte Antigen
Hematopoietic Stem Cell
Hematopoietic Stem Cell Transplant
Graft-versus-Host-Disease prophylaxis
Intrabone infusion

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists