Intra Bone Marrow Injection Of Unrelated Cord Blood Cells (CB01)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
ClinicalTrials.gov Identifier:
NCT00696046
First received: June 9, 2008
Last updated: NA
Last verified: June 2008
History: No changes posted
  Purpose

Compared to other stemcell sources cord blood (CB) is easier and safer to procure, has no donor attrition, a limitless supply, reduced viral transmission, less acute & chronic GVHD, is rich in hematopoietic progenitor cells, and immaturity of T-cell-mediated immunity. CB has delayed neutrophil and platelet engraftment, a prolonged immune reconstitution, uncertain graft-vs-tumor activity, and cell doses from single CB units (U) are a limiting factor for larger recipients Using the intravenous route (IV), a close match between the patient (pts) and the donor or CBU can improve a pts outcome after transplant. Even though a closely matched CBU is preferred, the studies suggest the match may not have to be as close as is needed for marrow or peripheral blood transplants If one has an uncommon tissue type, the doctor may not find a closely matched adult donor and a CBU may be an option, are stored and ready to use. GVHD is a complication after an allogeneic transplant. Studies founded that after a CBtransplant, fewer pts get GVHD than after marrow or peripheral blood transplants. Pts in the studies who did get GVHD after CBtransplant tended to get less severe cases We hypothesized that direct intrabone transplant of CBcells could improve haematologic recovery due to a better stem cell homing, based on the following observations: stem cells recirculate in animals irradiated with limb shielding; a limited fraction (10-15%) of cells injected iv to the haematopoietic sites, possibly because the large majority is lost in other organs; in a mousemodel, HSC directly injected ib repopulated the marrow of lethally irradiated mice 10times more efficiently than HSC cells injected iv; delayed engraftment after CB transplant is possibly not caused by insufficient stem cell numbers; indeed, children grafted with CB cells have superior stem cell reservoir 1year posttransplant when compared to marrow transplant recipients Based on these data, we set-up a phase I-II study to evaluate whether ib injection could be safely performed and whether this procedure could ensure engraftment and shorten the time of complete hematopoietic recovery in adults with high risk haematopoietic malignancies compared to the published data. Neutrophil recovery >80% at day60 and Platelets recovery >80% at days100 were defined as success. 1° endpoint was the probability of neutrophils and platelets recovery after ib CB transplant, 2° included incidence of acute GVHD, relapse, overall survival


Condition Intervention Phase
Hematologic Diseases
Procedure: Intrabone Marrow Injection
Phase 1
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: Direct Intra Bone Marrow Injection Of Unrelated Cord Blood Cells To Improve Engraftment And Reduce Acute Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:

Primary Outcome Measures:
  • the safety and the probability of neutrophils and platelets recovery after i.b. cord blood transplant. [ Time Frame: Full blood count, Monitoring Infections post Transplant, Bone marrow evaluation, Chimerism Analysis, Haematopoietic Reconstitution ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • the incidence/severity of acute Graft-versus-Host Disease, relapse and overall survival. [ Time Frame: Graft-versus-host disease was scored according to current criteria (13). ] [ Designated as safety issue: No ]

Estimated Enrollment: 47
Study Start Date: March 2006
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Intrabone Marrow Injection
    Cord blood CB units will be thawed in a 37° CB cells will be resuspended in 20ml salinesolution + dextran/albumin, and aliquoted in 4 syringes of 5ml Pts were prepared in a surgical & steril room The anaesthesia consist in a short propofol sedation The injection will last 8-15 minutes. 1° sedation is established, a standard needle for bone marrow aspiration (14 gauge) was inserted few cms in the supero-posterior iliac crest then, an aspiration of about 0.5-1 ml will be performed to assess that the needle was securely introduced in the bone marrow cavity After, we will insert the syringe containing 4-5ml of CB cell suspension which will be gently infused This procedure will be then repeated for all the remaining aliquots at a distance of 2-3cm from the previous one following the iliac crest
Detailed Description:

Study Design Phase I-II study. Neutrophil recovery > 80% at day 60 and Platelets recovery > 80% at days 100 are defined as success. The limit of 60 days for neutrophil recovery was chosen because it represents the time at which rescue with a second transplant is decided in case of failure to engraft; the day 100 for platelets recovery is taken corresponds to first form reported after transplant to the European Blood and Marrow Transplant Registry.

HLA-A and -B antigens will be identified by low resolution DNA typing, whereas HLA-DRB1 type was determined by high resolution DNA typing techniques. HLA-A, HLA-B, and HLA-DRB1 typing was used to select the most closely matched donor unit-recipient pair, with preference given to HLA-DRB1-matched unit

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with hematologic malignancies and other forms of hematologic diseases including aplastic anemia
  2. Patients will be eligible to enter the study when: A) an unrelated stem cell transplantation was indicated; b) no suitable unrelated HLA-matched donors will be identified in a clinically useful time-frame.
  3. Age 16-70
  4. Serum creatinine <1.5 mg/dL or Creatinine Clearance >50 ml/min
  5. Serum bilirubin <1.5 mg/dl, SGPT <3 x upper limit of normal
  6. Negative serology for HIV
  7. Central Venous access (Central KT) secured through an indwelling catheter.
  8. Life expectancy is not severely limited by concomitant illness.
  9. Written and signed informed consent

Exclusion Criteria:

  1. Acute Myocardial Infarction (AMI) within the last 12 months
  2. Positive pregnancy test
  3. Positive HIV serology
  4. Chronic renal insufficiency (Serum creatinine >1.5 mg/dl or creatinine cleareance <=50 ml/min)
  5. Patient has another progressive malignant disease or a history of other malignancies within 2 years prior to study entry.
  6. Severe psychiatric illness or any disorder that compromises ability to give truly informed consent for participation in this study.
  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: NCT00696046

Contacts
Contact: francesco Frassoni, MD +39 010 5553961 ext 3941 francesco.frassoni@hsanmartino.it

Locations
Italy
A.O. San Martino - Dep. Center Stem cells and cell therapy" Recruiting
Genoa, Italy, 16132
Principal Investigator: francesco frassoni, MD         
Sponsors and Collaborators
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Investigators
Principal Investigator: francesco frassoni, MD A.O. San martino
  More Information

No publications provided by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: francesco frassoni MD, A.O. Universitaria San Martino - Center Stem cells and cell therapy"
ClinicalTrials.gov Identifier: NCT00696046     History of Changes
Other Study ID Numbers: CB01-139
Study First Received: June 9, 2008
Last Updated: June 9, 2008
Health Authority: Italy: Ethics Committee

Keywords provided by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:
CORD BLOOD CELLS
INTRA BONE MARROW INJECTION
ENGRAFTMENT
transplants

Additional relevant MeSH terms:
Hematologic Diseases

ClinicalTrials.gov processed this record on October 19, 2014