Sickle Cell DiseasePhase 1/2NCT00777231
Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
A Phase 1/2 study testing Enriched Hematopoetic Stem Cell Infusion in people with Sickle Cell Disease, run by Talaris Therapeutics Inc. at 3 sites in United States.
Trial summary
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with Hemoglobinopathies to halt disease progression. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Enriched Hematopoetic Stem Cell Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2005to Aug 2013
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The following criteria are established to identify subjects with sickle cell disease (SCD) who have a high predicted morbidity and are at risk for early mortality. Subjects with S/S disease, S/C disease, Hemoglobin H disease, Alpha Thalassemia Major, Thalassemia Major (also known as Cooley's anemia) or S/B thalassemia and one or more of the following medical complications will be eligible:
- History of impaired neurological function and/or findings on Magnetic Resonance Image (MRI)/Magnetic Resonance Angiogram (MRA) that are associated with sickle cell disease
- More than 1 episode of acute chest syndrome with stage I or II pulmonary disease
- Osteonecrosis involving ≥ 2 joints
- Sickle cell nephropathy as evidenced by a glomerular filtration rate of 30% - 50% of the predicted normal
- Alloimmunization that is sufficient to interfere with the efficacy of chronic transfusion therapy
Show all 19Show fewer
- Chronic or recurrent priapism
- Major visual impairment in one or both eyes with bilateral proliferative retinopathy
- Persistent disabling pain (≥ 2 episodes per year) despite trials of chronic transfusion and/or hydroxyurea at recommended doses for at least 6 months duration
- Additional General Criteria:
- Subjects must also meet all of the following general inclusion criteria:
- Subjects must have a related donor (identical or mismatched for 1, 2 or 3 HLA- A, HLA-B or HLA-DR loci).
- Subjects must have adequate cardiopulmonary function as documented by a left ventricular ejection fraction ≥ 50% (or within normal limits per Institutional criteria) or a left ventricular shortening fraction Within normal limits (WNL) per Institutional criteria, without inotropic support. If Ejection fraction is 40-50%, the patient may be considered for participation if cleared by a Cardiologist.
- Subjects must have adequate pulmonary function as documented by Diffusing capacity of the lung for carbon monoxide (DLCO) and Forced expiratory volume in 1 second (FEV1)
- 50% predicted for age and size. If DLCO and FEV1 are between 40-50%, patient may be considered for participation if cleared by a Pulmonologist.
- Subjects must have adequate hepatic function as demonstrated by a serum albumin ≥ 3.0 mg/dL, and serum glutamic pyruvic transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times the upper limit of normal.
- Subjects must have adequate renal function as demonstrated by a serum creatinine ≤ 1.5 mg/dL. If serum creatinine is ≥ 1.5 mg/dL, then a creatinine clearance test must be done and the result 50% of normal.
- Subjects or legal guardians must give written informed consent, and subjects must assent where age and intellectually appropriate.
- There are no age limits for this protocol.
Who cannot join
- Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, could not tolerate transplantation.
- Severe impairment of functional performance as evidenced by a Karnofsky (patients ≥16 years old) or Lansky (children <16 years old) score <70%
- Stage III or IV sickle cell pulmonary disease
- Renal insufficiency (GFR < 25% of predicted normal for age)
- Subjects with a positive human immunodeficiency virus (HIV) antibody test result
- Subjects who are pregnant, as indicated by a positive serum human chorionic gonadotrophin (HCG) test
- Subjects of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site
- Subjects must not have had previous radiation therapy that would preclude total body irradiation (as determined by a radiation oncologist).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Duke University Medical Center
Durham, North Carolina, 27705
University of Louisville
Louisville, Kentucky, 40202
St. Christopher's Hospital for Children
Pittsburgh, Pennsylvania, 19134
About this study
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with Hemoglobinopathies to halt disease progression.
Read the detailed description
Hematopoietic stem cell transplantation (HSCT) is emerging as a therapeutic alternative for patients with sickle cell disease. Conventional HSCT therapy has been limited to extremely high-risk hemoglobinopathy patients. Those patients who may be difficult to identify before end-organ damage develops.
Also, conventional HSCT is only available to the minority of candidates who have Histocompatibility Leukocyte Antigen (HLA) identical siblings to donate bone marrow or mobilized peripheral blood stem cells.
This study proposes two important improvements over conventional HSCT:
- Donor peripheral blood or bone marrow will be processed via a new technology, which will deplete mature immune cells while enriching hematopoietic stem cells (HSC) and graft facilitating cells (FC).
- A reduced intensity recipient conditioning regimen will be used to promote mixed allogeneic chimerism, as opposed to full donor chimerism, following HSCT.
These two elements may significantly improve the benefit:risk ratio of HSCT for patients with hemoglobinopathies. Stem cell transplantation may become a more feasible option for patients that do not have HLA-identical siblings that can donate stem cells. Also, transplantation may be offered to patients earlier in the disease progression, before end-organ damage occurs.
- Conditions
- Sickle Cell Disease
- Being tested
- Enriched Hematopoetic Stem Cell Infusion
- Keywords
- Sickle Cell, Stem Cell, Tolerance, Bone Marrow Transplant, Total Body Irradiation (TBI), Apheresis, Aplastic Anemia, Hemoglobinopathies, Non Malignant
- Medical subject headings
- Anemia, Sickle Cell, Anemia, Aplastic, Hemoglobinopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enriched Hematopoetic Stem Cell InfusionBiological
Enriched Hematopoetic Stem Cell Infusion
| Study group | Role | What they receive |
|---|---|---|
| Sickle Cell Disease | Experimental | Recipients treated with an enriched hematopoetic stem cell infusion Receives: Biological: Enriched Hematopoetic Stem Cell Infusion |
| Non-Malignant Disorders | Experimental | Recipients treated with an enriched hematopoetic stem cell infusion Receives: Biological: Enriched Hematopoetic Stem Cell Infusion |
| Aplastic Anemia | Experimental | Recipients treated with an enriched hematopoetic stem cell infusion Receives: Biological: Enriched Hematopoetic Stem Cell Infusion |
| Sickle Cell Disease : Extended Protocol | Experimental | Recipients treated with an enriched hematopoetic stem cell infusion and Campath 1H conditioning Receives: Biological: Enriched Hematopoetic Stem Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment
Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.
Measured: From one month to three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2008 (estimated)
- Study startJan 2005
- Primary completionAug 2010
- Study completionAug 2013
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.
- 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
- Single group
- Model description
- No control group used, single group for each of four different disease groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Talaris Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Duke University, St. Christopher's Hospital for Children, The Western Pennsylvania Hospital, University of Florida, Medical College of Pennsylvania Hospital, Hahnemann University Hospital
- Responsible party
- Sponsor
- Investigators
- Suzanne T Ildstad, M.D., Study director, Talaris Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00777231
- Sponsor's protocol ID
- ICT-7621-042298
- Other IDs
- 549.02, 430.98, 445.98, 417.98, Pro00009281
- Status last verified
- Oct 2020
- First submitted
- 20 Oct 2008
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
- ClinicalTrials.gov ID
- NCT00777231
- Acronym / sponsor ID
- ICT-7621-042298
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell, Stem Cell, Tolerance, Bone Marrow Transplant, Total Body Irradiation (TBI), Apheresis, Aplastic Anemia, Hemoglobinopathies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Talaris Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Duke University, St. Christopher's Hospital for Children, The Western Pennsylvania Hospital, University of Florida, Medical College of Pennsylvania Hospital, Hahnemann University Hospital
- Study start
- Jan 2005
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 22 Oct 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.
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with Hemoglobinopathies to halt disease progression.
Detailed description
Hematopoietic stem cell transplantation (HSCT) is emerging as a therapeutic alternative for patients with sickle cell disease. Conventional HSCT therapy has been limited to extremely high-risk hemoglobinopathy patients. Those patients who may be difficult to identify before end-organ damage develops.
Also, conventional HSCT is only available to the minority of candidates who have Histocompatibility Leukocyte Antigen (HLA) identical siblings to donate bone marrow or mobilized peripheral blood stem cells.
This study proposes two important improvements over conventional HSCT:
- Donor peripheral blood or bone marrow will be processed via a new technology, which will deplete mature immune cells while enriching hematopoietic stem cells (HSC) and graft facilitating cells (FC).
- A reduced intensity recipient conditioning regimen will be used to promote mixed allogeneic chimerism, as opposed to full donor chimerism, following HSCT.
These two elements may significantly improve the benefit:risk ratio of HSCT for patients with hemoglobinopathies. Stem cell transplantation may become a more feasible option for patients that do not have HLA-identical siblings that can donate stem cells. Also, transplantation may be offered to patients earlier in the disease progression, before end-organ damage occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- No control group used, single group for each of four different disease groups
| Arm | Type | Receives |
|---|---|---|
| Sickle Cell Disease | Experimental | Biological: Enriched Hematopoetic Stem Cell InfusionRecipients treated with an enriched hematopoetic stem cell infusion |
| Non-Malignant Disorders | Experimental | Biological: Enriched Hematopoetic Stem Cell InfusionRecipients treated with an enriched hematopoetic stem cell infusion |
| Aplastic Anemia | Experimental | Biological: Enriched Hematopoetic Stem Cell InfusionRecipients treated with an enriched hematopoetic stem cell infusion |
| Sickle Cell Disease : Extended Protocol | Experimental | Biological: Enriched Hematopoetic Stem Cell InfusionRecipients treated with an enriched hematopoetic stem cell infusion and Campath 1H conditioning |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- The following criteria are established to identify subjects with sickle cell disease (SCD) who have a high predicted morbidity and are at risk for early mortality. Subjects with S/S disease, S/C disease, Hemoglobin H disease, Alpha Thalassemia Major, Thalassemia Major (also known as Cooley's anemia) or S/B thalassemia and one or more of the following medical complications will be eligible:
- History of impaired neurological function and/or findings on Magnetic Resonance Image (MRI)/Magnetic Resonance Angiogram (MRA) that are associated with sickle cell disease
- More than 1 episode of acute chest syndrome with stage I or II pulmonary disease
- Osteonecrosis involving ≥ 2 joints
- Sickle cell nephropathy as evidenced by a glomerular filtration rate of 30% - 50% of the predicted normal
Key exclusion criteria (8 listed)
- Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, could not tolerate transplantation.
- Severe impairment of functional performance as evidenced by a Karnofsky (patients ≥16 years old) or Lansky (children <16 years old) score <70%
- Stage III or IV sickle cell pulmonary disease
- Renal insufficiency (GFR < 25% of predicted normal for age)
- Subjects with a positive human immunodeficiency virus (HIV) antibody test result
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 |
|---|---|---|
| Enriched Hematopoetic Stem Cell InfusionEnriched Hematopoetic Stem Cell Infusion | Biological | Aplastic Anemia, Non-Malignant Disorders, Sickle Cell Disease, Sickle Cell Disease : Extended Protocol |
Primary outcome
Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment
Time frame: From one month to three years
Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.
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 14 Oct 2020.
- Individual participant dataSharing planned: Undecided
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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.
Suzanne T Ildstad, M.D. study director
Talaris Therapeutics Inc.
3 sites 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 Enriched Hematopoetic Stem Cell Infusion in people with Sickle Cell Disease, run by Talaris Therapeutics Inc. at 3 sites 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 19 inclusion and 8 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 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment (time frame: From one month to three years). 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 14 Oct 2020.