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Immunosuppressive Agent
Nonmyeloablative Stem Cell Transplant for Sickle Cell Anemia and Thalassemia
Phase 2
Waitlist Available
Led By Matthew M Hsieh, M.D.
Research Sponsored by National Heart, Lung, and Blood Institute (NHLBI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial Must have
-Age greater than or equal to 4 years
--E. Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline
Must not have
Major anticipated illness or organ failure incompatible with survival from PBSC transplant
ECOG performance status of 3 or more
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 2 years
Awards & highlights
No Placebo-Only Group
Summary
This trial tests if using low dose radiation and certain drugs can help patients with beta-thalassemia or sickle cell disease better accept donor stem cells. The treatment aims to suppress the immune system to reduce rejection of the new cells.
Who is the study for?
This trial is for people aged 4 and older with severe sickle cell disease or beta-thalassemia, who are at high risk of complications not improved by other treatments. They must have a matched family donor willing to donate stem cells. Exclusions include serious infections within the last month, pregnancy, lactation, or any major illness that could interfere with transplant survival.
What is being tested?
The study tests a new transplant method using low-dose radiation and immunosuppressive drugs (cyclophosphamide, pentostatin, sirolimus) to see if they help patients better accept donated stem cells. Participants will undergo various procedures including blood tests and bone marrow sampling before receiving the treatment in hospital.
What are the potential side effects?
Potential side effects may include reactions to medication like cyclophosphamide or alemtuzumab such as nausea and hair loss; organ inflammation from sirolimus; skin irritation from radiotherapy; immune system weakening leading to increased infection risk.
Eligibility Criteria
Inclusion Criteria
You may be eligible if you check “Yes” for the criteria belowSelect...
I am at least 4 years old.
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I have sickle cell-related liver issues with high ferritin or bilirubin levels.
Select...
I have kidney problems due to sickle cell disease, including high creatinine, low filtration rate, or need for dialysis.
Select...
I have a family donor who is a complete match for my transplant.
Select...
I have beta-thalassemia with moderate to severe iron overload.
Select...
I have severe sickle cell disease with major organ damage or complications not improved by current treatments.
Select...
I have had a stroke confirmed by an MRI or need regular transfusions due to artery issues in my brain.
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I have severe sickle cell disease not improved by standard treatments.
Select...
I have beta-thalassemia with significant iron overload.
Select...
I have had acute chest syndrome twice or once while on hydroxyurea.
Select...
My liver extends more than 2cm below my rib cage.
Select...
I've been hospitalized at least 3 times last year for pain crises, even while on treatment.
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I need regular blood transfusions and my hemoglobin doesn't improve much on hydroxurea.
Select...
I have had at least 2 long-lasting erections.
Exclusion Criteria
You may be eligible for the trial if you check “No” for criteria below:Select...
I do not have any major illnesses or organ failures that would make a stem cell transplant impossible.
Select...
I need considerable assistance and am unable to carry out any work activities.
Timeline
Screening ~ 3 weeks3 visits
Treatment ~ Varies
Follow Up ~ 2 years
Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~2 years
Treatment Details
Study Objectives
Study objectives can provide a clearer picture of what you can expect from a treatment.Primary study objectives
Number of Participants With Donor Red Cells at 2 Years Post Stem Cell Transplant
Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant
Secondary study objectives
Mean CD3+ Cell Dose
Mean CD34+ Cell Dose
Median Day to Neutrophil Recovery
+10 moreAwards & Highlights
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
Trial Design
3Treatment groups
Experimental Treatment
Group I: Participants with pre-existing antibodies and SCD or Beta-thalassemia receiving stem cell transplantExperimental Treatment5 Interventions
Participants with pre-existing antibodies and Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.
Group II: Human Leukocyte Antigens (HLA) Matched Related Stem Cell DonorExperimental Treatment1 Intervention
Participants received filgrastim to mobilize peripheral blood stem cells for apheresis collection. Collected stem cells of donor will then be infused to HLA matched sibling.
Group III: Female participants with SCD or Beta-thalassemia receiving stem cell transplant with male donorExperimental Treatment5 Interventions
Female participants with Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant with male donor. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Filgrastim
2000
Completed Phase 3
~3690
Alemtuzumab
2004
Completed Phase 4
~1880
Sirolimus
2013
Completed Phase 4
~2750
Cyclophosphamide
2010
Completed Phase 4
~2310
Pentostatin
2000
Completed Phase 3
~1300
Radiotherapy
2017
Completed Phase 3
~2610
Research Highlights
Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Common treatments in stem cell transplantation, such as low dose radiation, cyclophosphamide, pentostatin, and sirolimus, work by suppressing the recipient's immune system to enhance donor stem cell acceptance. Low dose radiation and cyclophosphamide reduce bone marrow activity and immune response, lowering the risk of rejection and graft-versus-host disease (GVHD).
Pentostatin depletes lymphocytes by inhibiting adenosine deaminase, while sirolimus prevents T-cell activation and proliferation. These mechanisms are vital for increasing the success of engraftment and minimizing complications in stem cell transplantation patients.
Curative therapies: Allogeneic hematopoietic cell transplantation from matched related donors using myeloablative, reduced intensity, and nonmyeloablative conditioning in sickle cell disease.
Curative therapies: Allogeneic hematopoietic cell transplantation from matched related donors using myeloablative, reduced intensity, and nonmyeloablative conditioning in sickle cell disease.
Find a Location
Who is running the clinical trial?
National Institutes of Health Clinical Center (CC)NIH
389 Previous Clinical Trials
30,879,680 Total Patients Enrolled
National Cancer Institute (NCI)NIH
13,938 Previous Clinical Trials
41,023,114 Total Patients Enrolled
National Heart, Lung, and Blood Institute (NHLBI)Lead Sponsor
3,938 Previous Clinical Trials
47,792,242 Total Patients Enrolled
Media Library
Eligibility Criteria:
This trial includes the following eligibility criteria:- I am at least 4 years old.I am eligible for hydroxyurea treatment or a stem cell transplant.I have sickle cell-related liver issues with high ferritin or bilirubin levels.I have kidney problems due to sickle cell disease, including high creatinine, low filtration rate, or need for dialysis.I have a family donor who is a complete match for my transplant.I have beta-thalassemia with moderate to severe iron overload.My condition is specific to the disease being studied.I have severe sickle cell disease with major organ damage or complications not improved by current treatments.I have had a stroke confirmed by an MRI or need regular transfusions due to artery issues in my brain.I have bone damage in 2 or more joints, it greatly affects my daily life, and my treatment isn't improving my blood levels.I have a family member who matches me closely for a stem cell donation and is willing to donate.I have severe sickle cell disease not improved by standard treatments.I do not have any major illnesses or organ failures that would make a stem cell transplant impossible.I haven't followed my iron removal treatment as prescribed since my first transfusion.I have beta-thalassemia with significant iron overload.I need considerable assistance and am unable to carry out any work activities.I have had acute chest syndrome twice or once while on hydroxyurea.My liver extends more than 2cm below my rib cage.I've been hospitalized at least 3 times last year for pain crises, even while on treatment.You have any of the following medical conditions:I need regular blood transfusions and my hemoglobin doesn't improve much on hydroxurea.I have had at least 2 long-lasting erections.This criterion is not related to any specific disease.
Research Study Groups:
This trial has the following groups:- Group 1: Female participants with SCD or Beta-thalassemia receiving stem cell transplant with male donor
- Group 2: Participants with pre-existing antibodies and SCD or Beta-thalassemia receiving stem cell transplant
- Group 3: Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.