Sickle Cell DiseasePhase 1/2NCT00730314
Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
A Phase 1/2 study testing Hematopoietic stem cell transplantation in people with Sickle Cell Disease and Thalassemia, run by Children's Hospital Los Angeles at 1 site in United States.
Trial summary
This is a clinical trial of bone marrow transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. Genetic diseases of blood cell include: Red blood cell defects e.g. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Sickle Cell Disease, Thalassemia, Anemia
- What is being tested?
- Hematopoietic stem cell transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Aug 2015
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Lethal or sublethal genetic disease of blood cells, who lack a fully histocompatible sibling or other family donor
- Genetic diseases that would be candidates for this protocol includes those that have been shown to benefit from allogeneic HSCT: Red blood cell defects, Leukocyte defects/ Primary immune deficiencies, Platelets defects, Metabolic/storage disorders and Stem cell defects.
- Renal: creatinine clearance or glomerular filtration rate (GFR) ≥50 ml/min/1.73m2 and not requiring dialysis.
- Pulmonary: FEV1, FVC and DLCO (corrected for hemoglobin) ≥ 50% predicted. if unable to perform pulmonary function tests, then O2 saturation ≥ 92% in room air.
- Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction ≥ 26%
- Hepatic: Bilirubin ≤3x upper limit of normal (ULN) and ALT and AST ≤ 5x for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome).
- Patients will be 0-21 years of age.
- Disease specific inclusion criteria (as applicable per protocol).
Who cannot join
- Recipients should not have any of the general exclusion criteria, and disease specific exclusion criteria when applicable.
- Patient with histocompatible sibling
- End-organ failure that precludes the ability to tolerate the transplant procedure, including the conditioning regimen.
- Creatinine clearance or GFR < 50 ml/min/1.73m2 or renal failure requiring dialysis.
- Congenital heart disease resulting in congestive heart failure.
- Severe residual CNS disease/impairment [(other than hemiplegia alone) e.g. coma or intractable seizures]
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- Ventilatory failure
- Major congenital anomalies that adversely affect survival, e.g. CNS malformations
- Lansky score < 40% or Karnofsky score < 60%
- HIV seropositivity
- Diagnosis of Fanconi's anemia, Severe Combined Immunodeficiency (SCID)
- Positive pregnancy test (For female patients in child bearing period)
- Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet clinical symptoms progress)
- Disease specific exclusion criteria (as applicable per protocol).
Trial locations and contacts
1 site in 1 country.
United States1 site
Children Hospital Los Angeles
Los Angeles, California, 90027
About this study
Official title: Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor
This is a clinical trial of bone marrow transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. Genetic diseases of blood cell include: Red blood cell defects e.g. hemoglobinopathies (sickle cell disease and thalassemia), Blackfan-Diamond anemia and congenital or chronic hemolytic anemias; White blood cells defects/immune deficiencies e.g. chronic granulomatous disease, Wiskott-Aldrich syndrome,Osteopetrosis, Kostmann's syndrome (congenital neutropenia), Hereditary Lymphohistiocytosis (HLH); Platelets defects e.g.Congenital amegakaryocytic thrombocytopenia; Metabolic/storage disorders e.g. leukodystrophies,mucopolysaccharidoses as Hurler disease;Stem cell defects e.g.reticular agenesis, among many other rare similar conditions.
The study treatment plan uses a new transplant treatment regimen that aims to try to decrease the acute toxicities and complications associated with the standard treatment plans and to improve outcome
The blood stem cells will be derived from either unrelated donor or unrelated umbilical cord blood.
Read the detailed description
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. The stem cells will be derived from a 1) matched unrelated donor (MUD) or 2) unrelated umbilical cord blood (UCB). Patients will receive a novel conditioning regimen with Busulfan, Cytoxan and Fludarabine (Bu/Cy/Flu) and either Alemtuzumab (Campath 1H) for recipients of a MUD or rabbit Antithymocyte Globulin (rATG) for recipients of unrelated UCB prior to hematopoietic stem cell transplant (HSCT).
It is hypothesized that reduced dosages of Cytoxan will decrease the acute toxicities associated with the standard chemotherapies of Busulfan and Cytoxan (i.e. sinusoidal obstructive syndrome (SOS), hemorrhagic cystitis and mucositis). And the addition of fludarabine to a conditioning regimen with myeloablative doses of Busulfan and reduced dosages of Cytoxan prior to HSCT will overcome the engraftment barrier posed by an intact immune system, which is seen in patients with a genetic disease.
- Conditions
- Sickle Cell Disease, Thalassemia, Anemia, Granuloma, Wiskott-Aldrich Syndrome, Chediak Higashi Syndrome
- Being tested
- Hematopoietic stem cell transplantation
- Keywords
- unrelated, BMT, HSCT, bone marrow transplantation, sickle cell disease, thalassemia, CGD, HLH, Blackfan-Diamond anemia, Hurler, leukodystrophy, LAD I, Genetic diseases, Red blood cell defects, Leukocyte defects and immune deficiencies, Hereditary Lymphohistiocytosis, chronic granulomatous disease, Wiskott-Aldrich syndrome, Chediak Higashi syndrome, CD40 ligand deficiency
- Medical subject headings
- Anemia, Sickle Cell, Thalassemia, Anemia, Granuloma, Wiskott-Aldrich Syndrome, Chediak-Higashi Syndrome, Osteopetrosis, Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hematopoietic stem cell transplantationProcedure or surgery
hematopoietic stem cell transplantation conditioning regimen depending on graft source
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Unrelated donor Receives: Procedure: Hematopoietic stem cell transplantation |
| 2 | Experimental | Cord Blood Receives: Procedure: Hematopoietic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
toxicities
Measured: 3 years
adverse events
Measured: 3 years
engraftment
Measured: 1 year
immune reconstitution
Measured: 3 years
overall and event free survival survival
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital Los AngelesThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hisham Abdel-Azim, Children's Hospital Los Angeles
- Investigators
- Hisham Abdel-Azim, MD, Principal investigator, Childrens Hospital Los Angeles, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00730314
- Sponsor's protocol ID
- CCI #07-00119
- Other IDs
- CHLA-#07-00119
- Status last verified
- Jun 2016
- First submitted
- 6 Aug 2008
- Last updated
- 23 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor
- ClinicalTrials.gov ID
- NCT00730314
- Acronym / sponsor ID
- CCI #07-00119
- Conditions
- Sickle Cell Disease, Thalassemia, Anemia, Granuloma, Wiskott-Aldrich Syndrome, Chediak Higashi Syndrome
- Keywords
- unrelated, BMT, HSCT, bone marrow transplantation, sickle cell disease, thalassemia, CGD, HLH
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 8 Aug 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.
This is a clinical trial of bone marrow transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. Genetic diseases of blood cell include: Red blood cell defects e.g. hemoglobinopathies (sickle cell disease and thalassemia), Blackfan-Diamond anemia and congenital or chronic hemolytic anemias; White blood cells defects/immune deficiencies e.g. chronic granulomatous disease, Wiskott-Aldrich syndrome,Osteopetrosis, Kostmann's syndrome (congenital neutropenia), Hereditary Lymphohistiocytosis (HLH); Platelets defects e.g.Congenital amegakaryocytic thrombocytopenia; Metabolic/storage disorders e.g. leukodystrophies,mucopolysaccharidoses as Hurler disease;Stem cell defects e.g.reticular agenesis, among many other rare similar conditions.
The study treatment plan uses a new transplant treatment regimen that aims to try to decrease the acute toxicities and complications associated with the standard treatment plans and to improve outcome
The blood stem cells will be derived from either unrelated donor or unrelated umbilical cord blood.
Detailed description
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling donor. The stem cells will be derived from a 1) matched unrelated donor (MUD) or 2) unrelated umbilical cord blood (UCB). Patients will receive a novel conditioning regimen with Busulfan, Cytoxan and Fludarabine (Bu/Cy/Flu) and either Alemtuzumab (Campath 1H) for recipients of a MUD or rabbit Antithymocyte Globulin (rATG) for recipients of unrelated UCB prior to hematopoietic stem cell transplant (HSCT).
It is hypothesized that reduced dosages of Cytoxan will decrease the acute toxicities associated with the standard chemotherapies of Busulfan and Cytoxan (i.e. sinusoidal obstructive syndrome (SOS), hemorrhagic cystitis and mucositis). And the addition of fludarabine to a conditioning regimen with myeloablative doses of Busulfan and reduced dosages of Cytoxan prior to HSCT will overcome the engraftment barrier posed by an intact immune system, which is seen in patients with a genetic disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Hematopoietic stem cell transplantationUnrelated donor |
| 2 | Experimental | Procedure: Hematopoietic stem cell transplantationCord Blood |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Lethal or sublethal genetic disease of blood cells, who lack a fully histocompatible sibling or other family donor
- Genetic diseases that would be candidates for this protocol includes those that have been shown to benefit from allogeneic HSCT: Red blood cell defects, Leukocyte defects/ Primary immune deficiencies, Platelets defects, Metabolic/storage disorders and Stem cell defects.
- Renal: creatinine clearance or glomerular filtration rate (GFR) ≥50 ml/min/1.73m2 and not requiring dialysis.
- Pulmonary: FEV1, FVC and DLCO (corrected for hemoglobin) ≥ 50% predicted. if unable to perform pulmonary function tests, then O2 saturation ≥ 92% in room air.
- Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening fraction ≥ 26%
Key exclusion criteria (14 listed)
- Recipients should not have any of the general exclusion criteria, and disease specific exclusion criteria when applicable.
- Patient with histocompatible sibling
- End-organ failure that precludes the ability to tolerate the transplant procedure, including the conditioning regimen.
- Creatinine clearance or GFR < 50 ml/min/1.73m2 or renal failure requiring dialysis.
- Congenital heart disease resulting in congestive heart failure.
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 |
|---|---|---|
| Hematopoietic stem cell transplantationhematopoietic stem cell transplantation conditioning regimen depending on graft source | Procedure or surgery | 1, 2 |
Primary outcome
toxicities
Time frame: 3 years
adverse events
Time frame: 3 years
engraftment
Time frame: 1 year
immune reconstitution
Time frame: 3 years
overall and event free survival survival
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2016.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Hisham Abdel-Azim, MD principal investigator
Childrens Hospital Los Angeles, University of Southern California
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 Hematopoietic stem cell transplantation in people with Sickle Cell Disease and Thalassemia, run by Children's Hospital Los Angeles at 1 site in United States.
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 8 inclusion and 14 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: finished, as of the sponsor's last update on 23 Jun 2016. 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 United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
toxicities (time frame: 3 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jun 2016.