Intra Bone Marrow Injection Of Unrelated Cord Blood Cells

NCT00696046 | Unknown Phase 1

• 1 other identifier: CB01-139
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hematologic Diseases

Keywords

CORD BLOOD CELLS; INTRA BONE MARROW INJECTION; ENGRAFTMENT; transplants

Outcome Measures

Primary Outcomes (1)

• the safety and the probability of neutrophils and platelets recovery after i.b. cord blood transplant.

  Full blood count, Monitoring Infections post Transplant, Bone marrow evaluation, Chimerism Analysis, Haematopoietic Reconstitution

Secondary Outcomes (1)

• the incidence/severity of acute Graft-versus-Host Disease, relapse and overall survival.

  Graft-versus-host disease was scored according to current criteria (13).

Interventions

Intrabone Marrow Injection PROCEDURE

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

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with hematologic malignancies and other forms of hematologic diseases including aplastic anemia
• 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.
• Age 16-70
• Serum creatinine \<1.5 mg/dL or Creatinine Clearance \>50 ml/min
• Serum bilirubin \<1.5 mg/dl, SGPT \<3 x upper limit of normal
• Negative serology for HIV
• Central Venous access (Central KT) secured through an indwelling catheter.
• Life expectancy is not severely limited by concomitant illness.
• Written and signed informed consent

You may not qualify if:

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

Sponsors & Collaborators

• IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy: lead

Study Sites (1)

A.O. San Martino - Dep. Center Stem cells and cell therapy"

Genoa, genoa, 16132, Italy

RECRUITING

Related Publications (1)

• Frassoni F, Gualandi F, Podesta M, Raiola AM, Ibatici A, Piaggio G, Sessarego M, Sessarego N, Gobbi M, Sacchi N, Labopin M, Bacigalupo A. Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study. Lancet Oncol. 2008 Sep;9(9):831-9. doi: 10.1016/S1470-2045(08)70180-3. Epub 2008 Aug 8.

  PMID: 18693069 DERIVED

MeSH Terms

Conditions

Hematologic Diseases

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Study Officials

• francesco frassoni, MD

  A.O. San martino

  PRINCIPAL INVESTIGATOR

Central Study Contacts

francesco Frassoni, MD

CONTACT

+39 010 5553961; francesco.frassoni@hsanmartino.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 9, 2008
• First Posted: June 12, 2008
• Study Start: March 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: June 1, 2009
• Last Updated: June 12, 2008

Record last verified: 2008-06

Locations

IT (1)