Hematologic DiseasesPhase 1/2CB01NCT00696046
Intra Bone Marrow Injection Of Unrelated Cord Blood Cells
A Phase 1/2 study testing Intrabone Marrow Injection in people with Hematologic Diseases, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Hematologic Diseases
- What is being tested?
- Intrabone Marrow Injection
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 47 participants
- Where
- 1 siteItaly
- Study dates
- Mar 2006to Jun 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- Central Venous access (Central KT) secured through an indwelling catheter.
- Life expectancy is not severely limited by concomitant illness.
- Written and signed informed consent
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
A.O. San Martino - Dep. Center Stem cells and cell therapy"
Genoa, genoa, 16132
francesco frassoni, MD
About this study
Official title: Direct Intra Bone Marrow Injection Of Unrelated Cord Blood Cells To Improve Engraftment And Reduce Acute Graft-Versus-Host Disease
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
Read the 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
- Conditions
- Hematologic Diseases
- Being tested
- Intrabone Marrow Injection
- Keywords
- CORD BLOOD CELLS, INTRA BONE MARROW INJECTION, ENGRAFTMENT, transplants
- Medical subject headings
- Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrabone Marrow InjectionProcedure or surgery
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
What is being measured
The primary outcome is the main question the study is designed to answer.
the safety and the probability of neutrophils and platelets recovery after i.b. cord blood transplant.
Measured: 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.
Measured: Graft-versus-host disease was scored according to current criteria (13).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2008 (estimated)
- Study startMar 2006
- Primary completionDec 2008 (estimated)
- Study completionJun 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Sponsor type
- University, hospital or other
- Investigators
- francesco frassoni, MD, Principal investigator, A.O. San martino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00696046
- Sponsor's protocol ID
- CB01-139
- Acronym
- CB01
- Status last verified
- Jun 2008
- First submitted
- 9 Jun 2008
- Last updated
- 12 Jun 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18693069
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct Intra Bone Marrow Injection Of Unrelated Cord Blood Cells To Improve Engraftment And Reduce Acute Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT00696046
- Acronym / sponsor ID
- CB01 / CB01-139
- Conditions
- Hematologic Diseases
- Keywords
- CORD BLOOD CELLS, INTRA BONE MARROW INJECTION, ENGRAFTMENT, transplants
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, ItalyUniversity, hospital or other
- Study start
- Mar 2006
- Primary completion
- Dec 2008 (estimated)
- Study completion
- Jun 2009 (estimated)
- First posted
- 12 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrabone Marrow InjectionCord 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 | Procedure or surgery | – |
Primary outcome
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
1 secondary outcome
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).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2008.
- Derived from this study: PubMed 18693069Frassoni 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
francesco frassoni, MD principal investigator
A.O. San martino
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Intrabone Marrow Injection in people with Hematologic Diseases, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jun 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact francesco Frassoni, MD (+39 010 5553961 ext. 3941, francesco.frassoni@hsanmartino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00696046, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2008.