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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by St. Orsola Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Francesca Bonifazi, MD, St. Orsola Hospital
ClinicalTrials.gov Identifier:
NCT00886522
First received: April 22, 2009
Last updated: June 7, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Hematological Malignancies
Procedure: Intrabone cord blood infusion
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intrabone Infusion of Cord Blood Hemopoietic Stem Cells in Adult Patients With High Risk Haematological Malignancies.

Resource links provided by NLM:


Further study details as provided by St. Orsola Hospital:

Primary Outcome Measures:
  • Proportion of transplanted patients with successful engraftment at day +42 [ Time Frame: Within the first 42 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical response with the analysis of global survival, survival without relapse, relapse incidence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Acute and chronic GVHD incidence [ Time Frame: For acute GVHD 100 days; for chronic GVHD 1 year ] [ Designated as safety issue: No ]
  • Infection incidence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Chimerism study on selected populations (myeloid, lymphoid, NK) [ Time Frame: 30, 60, 100 days, 6 months and 1 year ] [ Designated as safety issue: No ]
  • Studies on immunological reconstitution [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 17
Study Start Date: April 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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-RNA positive patients (it is possible to enrol them after discussion with the Principal Investigator).
  • Pregnant or lactating women.
  • Severe mental diseases.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00886522

Contacts
Contact: Francesca Bonifazi, MD +39-051-636-3835/3799 francesca.bonifazi@unibo.it
Contact: Maddalena Tonioli, PhD +39-051-636-3799 accreditamento.jacie@unibo.it

Locations
Italy
Hematology Institute "L. and A. Seràgnoli", S. Orsola-Malpighi University Hospital Recruiting
Bologna, Italy, 40138
Contact: Francesca Bonifazi, MD    +39-051-636-3835/3799    francesca.bonifazi@unibo.it   
Contact: Maddalena Tonioli, PhD    +39-051-636-3799    accreditamento.jacie@unibo.it   
Principal Investigator: Francesca Bonifazi, MD         
Sponsors and Collaborators
St. Orsola Hospital
Investigators
Principal Investigator: Francesca Bonifazi, MD S. Orsola-Malpighi University Hospital
  More Information

Additional Information:
Publications:
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.
Gluckman E, Rocha V, Boyer Chammard A et al. Outcome of cord blood transplantation from related and unrelated donors. NEJM 337:373-381, 1997.
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.
List A.L., Vardiman J., Jean-Pierre J. Issa, and DeWitte TM. Myelodysplastic Syndromes. Hematology 2004: 297-317.
Mayer RJ, David RD, Schiffer CA et al. Intensive post-remission chemotherapy in adults with acute myeloid leukemia NEJM 1994; 331: 896-903.
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
ClinicalTrials.gov Identifier: NCT00886522     History of Changes
Other Study ID Numbers: 152/2008/U/Sper
Study First Received: April 22, 2009
Last Updated: June 7, 2012
Health Authority: Italy: The Italian Medicines Agency
Italy: Ministry of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by St. Orsola Hospital:
Anti-thymocyte globulin Fresenius
Busulfan
Cord blood
Cyclophosphamide
Fludarabine
Human Leucocyte Antigen
Hematopoietic Stem Cell
Hematopoietic Stem Cell Transplant
Graft-versus-Host-Disease
Graft-versus-Host-Disease prophylaxis
Intrabone infusion
Thiotepa

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 23, 2014