Sickle Cell Disease and ThalassemiaPhase 2NCT02038478
Allograft for Sickle Cell Disease and Thalassemia
A Phase 2 study testing Donor Stem Cell Transplantation in people with Sickle Cell Disease and Thalassemia, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The design of the study incorporates the following features: 1. This is a phase II study to determine the safety and therapeutic potential of a new transplant approach (disease-free survival, graft versus myeloma effect) and to evaluate its toxicity profile (immediate toxicity, graft-versus-host disease, graft… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Sickle Cell Disease and Thalassemia
- What is being tested?
- Donor Stem Cell Transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2014to May 2021
- Phase
- Phase 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 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Disease specific:
- Sickle Cell Disease - Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having irreversible end-organ damage (A, B, C,D, or E) or potentially reversible complication(s) not ameliorated by hydroxyurea (F):
- Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI OR an abnormal trans-cranial Doppler examination (≥200m/s); OR
- Sickle cell related renal insufficiency defined by a creatinine level ≥1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance < 50mL/min OR requiring peritoneal or hemodialysis. OR
- Pulmonary hypertension as defined by tricuspid regurgitant jet velocity (TRV) of ≥ 2.5m/s at least 3 weeks after a vaso-occlusive crisis; OR
- Recurrent tricorporal priapism defined as at least two episodes of an erection lasting ≥4 hours involving the corpora cavernosa and corpus spongiosa; OR
Show all 23Show fewer
- Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline; OR
- Any one of the below complications
- Vaso-occlusive crises
- Acute chest syndrome
- Osteonecrosis of 2 or more joints
- Red cell alloimmunization
- Thalassemia - Patients with thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:
- portal fibrosis by liver biopsy inadequate chelation history (defined as failure to maintain adequate compliance with chelation with desferroxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-10 hours at least 5 days each week) hepatomegaly of greater than 2 cm below the costochondral margin
- Non-disease specific:
- Ages ≥ 18 but ≤ 45
- 6/6 HLA matched family donor available
- Ability to comprehend and willing to sign an informed consent, assent obtained from minors
- Negative serum pregnancy test
- 6/6 HLA identical family donor
- Weight > 20 kg (in so far that the weight difference between recipient and donor does not exceed a reasonable likelihood of being able to obtain an adequate cell dose from the donor within two aphereses)
- Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts, normotensive, and no history of stroke)
- Ability to comprehend and willing to sign an informed consent
Who cannot join
- Any of the following would exclude the subject from participating
- ECOG performance status of 3 or more or Lanksy performance status of <40
- Diffusion capacity of carbon monoxide (DLCO) <50% predicted (corrected for hemoglobin and alveolar volume)
- Baseline oxygen saturation of <85% or PaO2 <70
- Left ventricular ejection fraction: <40% estimated by ECHO
- Transaminases > 5x upper limit of normal for age
Show all 22Show fewer
- Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen
- Major anticipated illness or organ failure incompatible with survival from PBSC transplant
- Pregnant or lactating
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Major ABO mismatch
- Any of the following would exclude the donor from participating
- Pregnant or lactating
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- HIV positive
- Hemoglobin S > 50%, or beta thalassemia intermediate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Severe Congenital Anemias Including Sickle Cell Disease and Thalassemia
The design of the study incorporates the following features:
- This is a phase II study to determine the safety and therapeutic potential of a new transplant approach (disease-free survival, graft versus myeloma effect) and to evaluate its toxicity profile (immediate toxicity, graft-versus-host disease, graft rejection, mortality) in a patient population with severe congenital anemias.
- The patient cohort to be studied: Those patients with severe sickle cell disease and thalassemia who have risk factors for high mortality and morbidity related to their disease
- Transplant Conditioning Regimen - Immunosuppression without myeloablation: Patients will receive conditioning sufficient to allow donor lympho-hematopoietic engraftment without complete marrow ablation. If the graft is rejected, the patient will reconstitute autologous marrow function. We will use a combination of low dose irradiation, Alemtuzumab (Campath®), and sirolimus.
- Peripheral blood hematopoietic progenitor cell (PBPC) transplant: An unmanipulated peripheral blood stem cell collection from a filgrastim (G-CSF) stimulated HLA-matched donor should improve the chance of engraftment because of the high stem cell dose (5 x 106/kg CD34+ cells) and the presence of donor lymphocytes. To reduce the risk of GVHD, patients will receive sirolimus before and after the transplant. The sirolimus will be tapered as necessary to minimize any graft versus host disease while still maintaining adequate chimerism.
Read the detailed description
A human lymphocyte antigen (HLA)-matched sibling donor will receive filgrastim (G-CSF) 10 to16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of PBPC on day 5 (and day 6 if required). The product will be collected by leukophoresis with a goal of ≥ 10 x 106 CD34+ cells/kg, with a minimum of 5 x 106 CD34+ cells/kg.
The patient will receive a preparative regimen of Alemtuzumab to be infused on days -7 to -3, followed by 300 cGy TBI given as a single dose on day -2. Sirolimus at a dose of 5mg/day to maintain trough levels between 10-15ng/ml will be started on day -1. The PBPC graft targeted to deliver 10 x 106 CD34+ cells/kg (at minimum, 5 x 106 CD34+ cells/kg) will be infused on day 0 On days +14, +30, +60 and +100 the chimeric status of patients will be assessed by microsatellite analysis of the peripheral blood. More frequent monitoring may be required.
Sickle cell patients with pulmonary hypertension will meet with a Pulmonary Medicine Consult to determine appropriate management prior to SCT.
Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.
Iron chelation must be discontinued > 48 hours before initiating the conditioning regimen.
Hydroxyurea must be discontinued one day prior to initiating the conditioning regimen.
- Conditions
- Sickle Cell Disease and Thalassemia
- Being tested
- Donor Stem Cell Transplantation
- Keywords
- Sickle Cell Disease, Thalassemia
- Medical subject headings
- Anemia, Sickle Cell, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor Stem Cell TransplantationBiological
One day after they complete their radiation and Campath-1H treatments and have begun their Sirolimus, the donor blood stem cells described above are transfused through the central line. This process takes approximately 30 minutes to 2 hours and is normally completely without side effects.
| Study group | Role | What they receive |
|---|---|---|
| Transplantation Arm | Experimental | Transplantation
One day after they complete their radiation and Campath-1H treatments and have begun their Sirolimus, the donor blood stem cells described above are transfused through the central line. This process takes approximately 30 minutes to 2 hours and is normally completely without side effects. Receives: Biological: Donor Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Success at One Year
This is defined as full donor type hemoglobin on hemoglobin electrrophoresis for patients with sickle cell disease and transfusion-independence for patients with thalassemia.
Measured: Treatment Success at one year
Secondary outcomes (1)
Level of chierism required to maintain Graft Survival and hematologic normalcy
The chimeric status of patients will be measured on days +14, +30, +60, and +100 by microsatellite analysis of the peripheral blood.
Measured: Measured on days 14, 30, 60 and 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionJan 2021 (estimated)
- Study completionMay 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell Disease and ThalassemiaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prapti Patel, University of Texas Southwestern Medical Center
- Investigators
- Prapti Patel, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02038478
- Sponsor's protocol ID
- STU 012013-015
- Status last verified
- Jul 2021
- First submitted
- 10 Jan 2014
- Last updated
- 29 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Severe Congenital Anemias Including Sickle Cell Disease and Thalassemia
- ClinicalTrials.gov ID
- NCT02038478
- Acronym / sponsor ID
- STU 012013-015
- Conditions
- Sickle Cell Disease and Thalassemia
- Keywords
- Sickle Cell Disease, Thalassemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Jan 2021 (estimated)
- Study completion
- May 2021 (actual)
- First posted
- 16 Jan 2014 (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 design of the study incorporates the following features:
- This is a phase II study to determine the safety and therapeutic potential of a new transplant approach (disease-free survival, graft versus myeloma effect) and to evaluate its toxicity profile (immediate toxicity, graft-versus-host disease, graft rejection, mortality) in a patient population with severe congenital anemias.
- The patient cohort to be studied: Those patients with severe sickle cell disease and thalassemia who have risk factors for high mortality and morbidity related to their disease
- Transplant Conditioning Regimen - Immunosuppression without myeloablation: Patients will receive conditioning sufficient to allow donor lympho-hematopoietic engraftment without complete marrow ablation. If the graft is rejected, the patient will reconstitute autologous marrow function. We will use a combination of low dose irradiation, Alemtuzumab (Campath®), and sirolimus.
- Peripheral blood hematopoietic progenitor cell (PBPC) transplant: An unmanipulated peripheral blood stem cell collection from a filgrastim (G-CSF) stimulated HLA-matched donor should improve the chance of engraftment because of the high stem cell dose (5 x 106/kg CD34+ cells) and the presence of donor lymphocytes. To reduce the risk of GVHD, patients will receive sirolimus before and after the transplant. The sirolimus will be tapered as necessary to minimize any graft versus host disease while still maintaining adequate chimerism.
Detailed description
A human lymphocyte antigen (HLA)-matched sibling donor will receive filgrastim (G-CSF) 10 to16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of PBPC on day 5 (and day 6 if required). The product will be collected by leukophoresis with a goal of ≥ 10 x 106 CD34+ cells/kg, with a minimum of 5 x 106 CD34+ cells/kg.
The patient will receive a preparative regimen of Alemtuzumab to be infused on days -7 to -3, followed by 300 cGy TBI given as a single dose on day -2. Sirolimus at a dose of 5mg/day to maintain trough levels between 10-15ng/ml will be started on day -1. The PBPC graft targeted to deliver 10 x 106 CD34+ cells/kg (at minimum, 5 x 106 CD34+ cells/kg) will be infused on day 0 On days +14, +30, +60 and +100 the chimeric status of patients will be assessed by microsatellite analysis of the peripheral blood. More frequent monitoring may be required.
Sickle cell patients with pulmonary hypertension will meet with a Pulmonary Medicine Consult to determine appropriate management prior to SCT.
Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.
Iron chelation must be discontinued > 48 hours before initiating the conditioning regimen.
Hydroxyurea must be discontinued one day prior to initiating the conditioning regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplantation Arm | Experimental | Biological: Donor Stem Cell TransplantationTransplantation One day after they complete their radiation and Campath-1H treatments and have begun their Sirolimus, the donor blood stem cells described above are transfused through the central line. This process takes approximately 30 minutes to 2 hours and is normally completely without side effects. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- Sickle Cell Disease - Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having irreversible end-organ damage (A, B, C,D, or E) or potentially reversible complication(s) not ameliorated by hydroxyurea (F):
- Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI OR an abnormal trans-cranial Doppler examination (≥200m/s); OR
- Sickle cell related renal insufficiency defined by a creatinine level ≥1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance < 50mL/min OR requiring peritoneal or hemodialysis. OR
- Pulmonary hypertension as defined by tricuspid regurgitant jet velocity (TRV) of ≥ 2.5m/s at least 3 weeks after a vaso-occlusive crisis; OR
- Recurrent tricorporal priapism defined as at least two episodes of an erection lasting ≥4 hours involving the corpora cavernosa and corpus spongiosa; OR
Key exclusion criteria (22 listed)
- Any of the following would exclude the subject from participating
- ECOG performance status of 3 or more or Lanksy performance status of <40
- Diffusion capacity of carbon monoxide (DLCO) <50% predicted (corrected for hemoglobin and alveolar volume)
- Baseline oxygen saturation of <85% or PaO2 <70
- Left ventricular ejection fraction: <40% estimated by ECHO
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 |
|---|---|---|
| Donor Stem Cell TransplantationOne day after they complete their radiation and Campath-1H treatments and have begun their Sirolimus, the donor blood stem cells described above are transfused through the central line. This process takes approximately 30 minutes to 2 hours and is normally completely without side effects. | Biological | Transplantation Arm |
Primary outcome
Treatment Success at One Year
Time frame: Treatment Success at one year
This is defined as full donor type hemoglobin on hemoglobin electrrophoresis for patients with sickle cell disease and transfusion-independence for patients with thalassemia.
1 secondary outcome
Level of chierism required to maintain Graft Survival and hematologic normalcy
Time frame: Measured on days 14, 30, 60 and 100
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2021.
Related trials for Sickle Cell Disease and Thalassemia
Active, not recruitingObservational study
Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
Sickle Cell Anemia, Sickle Cell Thalassemia
Enrolling by invitationPhase 4
A Study to Provide Access to Mitapivat for Participants Who Previously Participated in an Agios-Sponsored Mitapivat Study
Pyruvate Kinase Deficiency, Anemia, Hemolytic
RecruitingPhase 1/2
Repeat Peripheral Blood Stem Cell Transplantation for Patients With Sickle Cell Disease and Falling Donor Myeloid Chimerism Levels
Myeloid Chimerism
RecruitingPhase 2
AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
Acute Leukemia, Severe Aplastic Anemia
RecruitingPhase 1/2
Partial Stem Cell Transplant for Sickle Cell Disease From Matched Donors
Sickle Cell Disease, Beta-thalassemia
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.
Prapti Patel, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Donor Stem Cell Transplantation in people with Sickle Cell Disease and Thalassemia, run by University of Texas Southwestern Medical Center 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 23 inclusion and 22 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: withdrawn, as of the sponsor's last update on 29 Jul 2021. 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 phase mean?
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 was withdrawn before enrolling participants, so there are no results.
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?
Treatment Success at One Year (time frame: Treatment Success at one year). 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 29 Jul 2021.