Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 14-H-0077 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Institutes of Health Clinical Center (CC) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Background:
- Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want to test a variation of transplant that uses low dose radiation and a combination of immunosuppressive drugs. They want to know if it helps a body to better accept donor stem cells.
Objectives:
- To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus help a body to better accept donor stem cells.
Eligibility:
- People 4 and older with beta-thalassemia or sickle cell disease that can be cured with transplant, and their donors.
Design:
Our ongoing nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplant protocol (03-H-0170) for patients with severe sickle cell disease (SCD) and B-thalassemia from HLA-matched family donors has excellent results thus far. Our long term leukocyte engraftment rate is 85-90% with the same disease-free survival. None of the engrafted patients had acute sickle-related events, significant toxicity associated with the conditioning regimen, or any evidence of graft versus host disease (GVHD).
While these results rival the transplant outcomes from low risk transplant patients with B-thalassemia, there are areas for improvement. The first is the 10-15% graft rejection rate, where a majority of these individuals were male donor and female recipient pairs. Another limitation is the significant delay in donor red cell engraftment in one recipient who had pre-existing allo-antibody to donor red cells from previous transfusions. Also we have excluded another group of individuals with preformed antibodies, recipients having major ABO incompatibility to the donors.
To overcome these limitations (and reduce the transplant failure rate) in this new protocol, we will continue our nonmyeloablative approach in the patients with SCD and B-thalassemia with HLA-matched family donors, but using an increased intensity regimen in a subset considered at high risk for transplant failure. This modified regimen consists of pentostatin and oral cyclophosphamide, which we hypothesize will reduce both the T cells that mediate leukocyte rejection and the B/plasma cells that produce anti-donor erythrocyte antibodies. The main transplant backbone will remain as alemtuzumab, low dose total body irradiation of 300 cGy, and sirolimus; the transplant graft will remain as unmanipulated G-CSF mobilized, T-cell replete, PBSC product for hematopoietic and lymphoid reconstitution.
The primary endpoint of this study is the percentage/number of patients who have sustained donor type hemoglobin at 1 year post transplant for male donors - female recipients. The primary endpoint for those with pre-existing antibodies is the presence of donor red cells with reticulocytes greater than or equal to 30 k/uL at 2 years post-transplant. Other endpoints include the toxicity of the pentostatin-cyclophosphamide regimen, the degree of donor-host chimerism necessary for long-term graft survival and disease amelioration, incidence of acute and chronic GVHD, incidence of graft rejection, transplant-related morbidity, as well as disease-free and overall survival. Since SCD and B-thalassemia are non-malignant disorders of red cells, severe GVHD, lack of donor erythrocyte (prolonged donor red cell aplasia), or graft rejection is collectively considered transplant failure.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Female participants with SCD or Beta-thalassemia receiving stem cell transplant with male donor | Experimental | 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. |
|
| Participants with pre-existing antibodies and SCD or Beta-thalassemia receiving stem cell transplant | Experimental | 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. |
|
| Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor | Other | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alemtuzumab | Drug | Immunosuppressant |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant | Number of patients who have sustained donor type hemoglobin at one year post transplant. Sustained donor type hemoglobin is based on hemoglobin electrophoresis for patients with SCD and transfusion independence for patients with beta-thalassemia | 1 year |
| Number of Participants With Donor Red Cells at 2 Years Post Stem Cell Transplant | Number of participants with donor red cells at 2 years post stem cell transplant. Number of participants with donor red cells is detected by hemoglobin electrophoresis or donor type red cell antigen, and reticulocyte count ≥30 k/uL at 2 years post-transplant. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Mean CD34+ Cell Dose | Mean CD34+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected | Day 0 up to Day 1 |
| Mean CD3+ Cell Dose | Mean CD3+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected |
Not provided
-INCLUSION CRITERIA- recipients (must fulfill one disease category in 1 and all of 2)
Disease specific
Patients with severe sickle cell disease (not limited to Hb SS, SC, or S beta-thal) at high risk for disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, C, D, or E) or potentially modifiable complication(s) not ameliorated by hydroxyurea or sickle specific therapy (F):
--A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy; OR
--B. Sickle cell-related renal insufficiency defined by a creatinine level greater than or equal to 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance less than < 50mL/min OR requiring peritoneal or hemodialysis; OR
--C. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5 m/s 40, 41 at baseline; OR
--D. Recurrent priapism defined as at least 2 episodes of an erection lasting >4 hours involving the corpora cavernosa and corpus spongiosa; OR
--E. Sickle hepatopathy defined as EITHER ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline
--F. Any one of the below complications:
---Complication/ Eligible for hydroxyurea*/ Eligible for HSCT
----Vaso-occlusive crises/ At least 3 hospital admissions in the last year/ More than one hospital admission in the last year while on therapeutic dose of hydroxyurea or sickle cell therapy
Acute chest syndrome/ 2 prior ACS/ any ACS while on hydroxyurea
Osetonecrosis of 2 or more joints/ And significantly affecting their quality of life by Karnofsky score 50-60/ And on hydroxyurea where total hemoglobuin increases less than 1 g/dL or fetal hemoglobin increases less than 2.5 times the baseline level
Red cell alloimmunization/ Transfusion dependent/ Total hemoglobin increases less than 1g/dL while on hydroxurea
2. Patients with beta-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
Non-disease specific:
-Age greater than or equal to 4 years
-6/6 HLA matched family donor available
EXCLUSION CRITERIA -recipient (any of the following would exclude the subject from participating)
-ECOG performance status of 3 or more
-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. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.
-Major anticipated illness or organ failure incompatible with survival from PBSC transplant
-Pregnant or lactating
INCLUSION CRITERIA -donor
-6/6 HLA matched family donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Matched related donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all matched related donors, but is not required for a donor to make a stem cell donation, so it is possible that not all related donors will enroll onto this study.
EXCLUSION CRITERIA -donor
-None
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Matthew M Hsieh, M.D. | National Heart, Lung, and Blood Institute (NHLBI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42133908 | Derived | Kern KC, Inam Z, Hsieh MM, Tisdale JF, Fitzhugh CD, Limerick EM, Gebremeskel ASK, White T, Jordan LC, Lynch JK. Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease. Neurology. 2026 Jun 9;106(11):e218050. doi: 10.1212/WNL.0000000000218050. Epub 2026 May 14. | |
| 40010689 | Derived |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
Not provided
All IPD that underlie results in a publication
At the time of publication or by the end of the protocol, whichever comes first, and available indefinitely
Data will be shared upon request by sending a request to matthewhs@nhlbi.nih.gov
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | 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. Alemtuzumab: Immunosuppressant Sirolimus: Immunosuppressant Cyclophosphamide: Immunosuppressant Pentostatin: Immunosuppressant Radiotherapy: Immunosuppressant and myelosuppressant |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 13, 2024 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Sirolimus | Drug | Immunosuppressant |
|
|
| Cyclophosphamide | Drug | Immunosuppressant |
|
|
| Pentostatin | Drug | Immunosuppressant |
|
|
| Radiotherapy | Procedure | Immunosuppressant and myelosuppressant |
|
| Filgrastim | Drug | mobilize peripheral blood stem cells for apheresis collection |
|
|
| Day 0 up to Day 1 |
| Median Percent of Donor T-cells and Myeloid Chimerism | Median Percent of donor T-cells and myeloid chimerism. Leukocytes are selected by magnetic beads for CD3 (T-cells) and CD14/15 (myeloid cells), then microsatellite PCR analyses are performed to obtain donor chimerism percent. | day 30, day 60 , day 100, 1 year and 2 year |
| Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Grades are defined as: Grade I: Skin = Maculopapular rash< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day. Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day. Grade III: Skin = Rash on >50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea > 1500 mL/day. Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin >15 mg/dL; Lower GI = Severe abdominal pain with or without ileus. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. | Up to Day 100 |
| Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) | Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) up to 5 years. Moderate chronic GVHD involves EITHER 3 organs/sites with no clinically significant functional impairment OR a less than or equal to 1 organ/site with clinically significant functional impairment, but no major disability. Severe GVHD is associated with a major disability caused by chronic GVHD. | Day 100 up to 2 years |
| Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant | Number of participants that experienced graft failure or graft rejection, or red cell aplasia at 2 years after transplant. Graft failure or graft rejection is defined as <5% donor cells in both CD3 and myeloid chimerism. Red cell aplasia is defined as reticulocyte <30 k/uL and requiring red cell transfusions. | Up to 2 years |
| Number of Participants That Experienced Regimen Failure | Number of Participants That Experienced Regimen Failure. Regimen failure is defined as those participants that experienced grade 3 or higher acute GVHD, moderate/severe chronic GVHD, graft failure/rejection, or red cell aplasia. Together any one of these count toward the combined endpoint of regimen failure. | Up to 2 years |
| Number of Participants That Experienced Transplant-related Mortality | Number of participants that experienced transplant-related mortality. Transplant-related mortality is defined as death that is at least possibly related to the transplant (GVHD, toxicity, infection, other causes). | Up to 2 years |
| Percentage of Participant With Disease-free Survival Following Stem Cell Transplant | Percentage of participant with disease-free survival following stem cell transplant. Disease-free survival is defined as alive and free acute complications related to sickle cell disease. | Up to 2 years |
| Percentage of Participant Overall Survival Following Stem Cell Transplant | Percentage of Participant Overall Survival up to year 2 following stem cell transplant. Overall survival is defined as being alive following stem cell transplant. | Up to 2 years |
| Median Day to Neutrophil Recovery | Median Day to Neutrophil recovery. Neutrophil recovery is defined as the first of three consecutive days of neutrophil count >0.5 x 10^9 cells/uL. | Up to Day 100 |
| Median Days to Platelet Recovery | Median Days to Platelet Recovery. Platelet recovery is defined as count >50 cells/uL and 7 days from the last platelet transfusion. | Up to Day 120 |
| Median Days to Red Cell Recovery | Median Days to Red Cell Recovery. Red cell recovery defined as days to recovery of reticulocyte count .30 k/uL, detection of donor red cells, transfusion independence. | Up to 2 years |
| Inam Z, Jeffries N, Link M, Coles W, Pollack P, Luckett C, Phang O, Harvey E, Martin T, Farrey T, Tisdale JF, Hsieh MM. Two Nonmyeloablative HLA-Matched Related Donor Allogeneic Hematopoietic Cell Transplantation Regimens in Patients with Severe Sickle Cell Disease. Transplant Cell Ther. 2025 May;31(5):305-318. doi: 10.1016/j.jtct.2025.02.021. Epub 2025 Feb 24. |
| 36240296 | Derived | Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137. |
| FG001 | Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | 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. Alemtuzumab: Immunosuppressant Sirolimus: Immunosuppressant Cyclophosphamide: Immunosuppressant Pentostatin: Immunosuppressant Radiotherapy: Immunosuppressant and myelosuppressant |
| FG002 | Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor | 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. Filgrastim: mobilize peripheral blood stem cells for apheresis collection |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | 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. Alemtuzumab: Immunosuppressant Sirolimus: Immunosuppressant Cyclophosphamide: Immunosuppressant Pentostatin: Immunosuppressant Radiotherapy: Immunosuppressant and myelosuppressant |
| BG001 | Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | 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. Alemtuzumab: Immunosuppressant Sirolimus: Immunosuppressant Cyclophosphamide: Immunosuppressant Pentostatin: Immunosuppressant Radiotherapy: Immunosuppressant and myelosuppressant |
| BG002 | Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor | 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. Filgrastim: mobilize peripheral blood stem cells for apheresis collection |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant | Number of patients who have sustained donor type hemoglobin at one year post transplant. Sustained donor type hemoglobin is based on hemoglobin electrophoresis for patients with SCD and transfusion independence for patients with beta-thalassemia | Analysis is intended per protocol for cohort 1 participants that received a stem cell transplant (female participants with male donors) | Posted | Count of Participants | Participants | 1 year |
|
|
| ||||||||||||||||||||||||||
| Primary | Number of Participants With Donor Red Cells at 2 Years Post Stem Cell Transplant | Number of participants with donor red cells at 2 years post stem cell transplant. Number of participants with donor red cells is detected by hemoglobin electrophoresis or donor type red cell antigen, and reticulocyte count ≥30 k/uL at 2 years post-transplant. | Analysis is intended per protocol to include those participants from cohort 2 (patients with pre-existing antibody to donor red cells) | Posted | Count of Participants | Participants | 2 years |
|
| |||||||||||||||||||||||||||
| Secondary | Mean CD34+ Cell Dose | Mean CD34+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected | Posted | Mean | Standard Deviation | x10^6 cells/kg | Day 0 up to Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | Mean CD3+ Cell Dose | Mean CD3+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected | Posted | Mean | Standard Deviation | x10^8 cells/kg | Day 0 up to Day 1 |
| ||||||||||||||||||||||||||||
| Secondary | Median Percent of Donor T-cells and Myeloid Chimerism | Median Percent of donor T-cells and myeloid chimerism. Leukocytes are selected by magnetic beads for CD3 (T-cells) and CD14/15 (myeloid cells), then microsatellite PCR analyses are performed to obtain donor chimerism percent. | Analysis includes those participants who have sustained engraftment or did not experience graft failure. | Posted | Median | Full Range | percentage of donor cells | day 30, day 60 , day 100, 1 year and 2 year |
| |||||||||||||||||||||||||||
| Secondary | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Grades are defined as: Grade I: Skin = Maculopapular rash< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day. Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day. Grade III: Skin = Rash on >50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea > 1500 mL/day. Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin >15 mg/dL; Lower GI = Severe abdominal pain with or without ileus. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. | Analysis includes those participants who have sustained engraftment or did not experience graft failure. | Posted | Count of Participants | Participants | Up to Day 100 |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) | Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) up to 5 years. Moderate chronic GVHD involves EITHER 3 organs/sites with no clinically significant functional impairment OR a less than or equal to 1 organ/site with clinically significant functional impairment, but no major disability. Severe GVHD is associated with a major disability caused by chronic GVHD. | Analysis includes those participants who have sustained engraftment or did not experience graft failure. | Posted | Count of Participants | Participants | Day 100 up to 2 years |
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant | Number of participants that experienced graft failure or graft rejection, or red cell aplasia at 2 years after transplant. Graft failure or graft rejection is defined as <5% donor cells in both CD3 and myeloid chimerism. Red cell aplasia is defined as reticulocyte <30 k/uL and requiring red cell transfusions. | Posted | Count of Participants | Participants | Up to 2 years |
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants That Experienced Regimen Failure | Number of Participants That Experienced Regimen Failure. Regimen failure is defined as those participants that experienced grade 3 or higher acute GVHD, moderate/severe chronic GVHD, graft failure/rejection, or red cell aplasia. Together any one of these count toward the combined endpoint of regimen failure. | Posted | Count of Participants | Participants | Up to 2 years |
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants That Experienced Transplant-related Mortality | Number of participants that experienced transplant-related mortality. Transplant-related mortality is defined as death that is at least possibly related to the transplant (GVHD, toxicity, infection, other causes). | Posted | Count of Participants | Participants | Up to 2 years |
| |||||||||||||||||||||||||||||
| Secondary | Percentage of Participant With Disease-free Survival Following Stem Cell Transplant | Percentage of participant with disease-free survival following stem cell transplant. Disease-free survival is defined as alive and free acute complications related to sickle cell disease. | Posted | Count of Participants | Participants | Up to 2 years |
| |||||||||||||||||||||||||||||
| Secondary | Percentage of Participant Overall Survival Following Stem Cell Transplant | Percentage of Participant Overall Survival up to year 2 following stem cell transplant. Overall survival is defined as being alive following stem cell transplant. | Posted | Count of Participants | Participants | Up to 2 years |
| |||||||||||||||||||||||||||||
| Secondary | Median Day to Neutrophil Recovery | Median Day to Neutrophil recovery. Neutrophil recovery is defined as the first of three consecutive days of neutrophil count >0.5 x 10^9 cells/uL. | Posted | Median | Full Range | days | Up to Day 100 |
| ||||||||||||||||||||||||||||
| Secondary | Median Days to Platelet Recovery | Median Days to Platelet Recovery. Platelet recovery is defined as count >50 cells/uL and 7 days from the last platelet transfusion. | Posted | Median | Full Range | days | Up to Day 120 |
| ||||||||||||||||||||||||||||
| Secondary | Median Days to Red Cell Recovery | Median Days to Red Cell Recovery. Red cell recovery defined as days to recovery of reticulocyte count .30 k/uL, detection of donor red cells, transfusion independence. | Posted | Median | Full Range | days | Up to 2 years |
|
5 years
Information on AEs will be solicited from subjects through questions from study personnel and/or information volunteered by the subject. Grade 3 or higher adverse event recording will start at the time of conditioning regimen, will be followed until satisfactory resolution, through final study visit.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | 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. Alemtuzumab: Immunosuppressant Sirolimus: Immunosuppressant Cyclophosphamide: Immunosuppressant Pentostatin: Immunosuppressant Radiotherapy: Immunosuppressant and myelosuppressant | 1 | 11 | 9 | 11 | 11 | 11 |
| EG001 | Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | 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. Alemtuzumab: Immunosuppressant Sirolimus: Immunosuppressant Cyclophosphamide: Immunosuppressant Pentostatin: Immunosuppressant Radiotherapy: Immunosuppressant and myelosuppressant | 1 | 18 | 13 | 18 | 18 | 18 |
| EG002 | Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor | 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. Filgrastim: mobilize peripheral blood stem cells for apheresis collection | 0 | 27 | 2 | 27 | 0 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Avascular necrosis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Bacteremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Clostridioides difficile colitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Cytomegalovirus (CMV) Reactivation | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Epstein-Barr virus (EBV) viremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Micro Papillary Thyroid Carcinoma | Endocrine disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Gastroparesis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Herpes simplex reactivation | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypokalemia | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Typhoid fever | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Malaria | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Joint effusion | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Meningitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Procedural pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Vaso-occlusive pain crisis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Psychosis | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Reversible posterior leukoencephalopathy syndrome | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Furunculosis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Sleep apnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Liver biopsy | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Plasma exchange | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Teeth extractions | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Hip replacement | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Tunneled catheter removal | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Tunneled line insertion | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Wound care | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Treatment related secondary malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
| |
| White blood cell decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Wound infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Headache | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Emesis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypocalcemia | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Hypomagnesemia | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Hypophosphatemia | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute GVHD | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| CD4 lymphocytes decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hemolysis | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Platelet count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| White blood cell decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypertension | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cataract | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Eye pain | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hemianopsia | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anal fistula | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Gastroparesis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Agitation | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Chills | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infusion related reaction | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Nausea | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypogammaglobulinemia | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anorectal infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Cytomegalovirus (CMV) Reactivation | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Endocarditis infective | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| BK Virus Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Methicillin-resistant Staphylococcus aureus (MRSA) infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Nasal vestibulitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Hyperuricemia | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Hypokalemia | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Hypophosphatemia | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Hypermagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Iron overload | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Obesity | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Obsessive-compulsive disorder (OCD) | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pseudoseizure | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Right Heart Catheterization | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Thyroidectomy | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Hot flashes | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lymphedema | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Matthew Hsieh M.D. | National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI) | 301.402.7687 | matthewhs@nhlbi.nih.gov |
| Sep 27, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D013789 | Thalassemia |
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000074323 | Alemtuzumab |
| D020123 | Sirolimus |
| D003520 | Cyclophosphamide |
| D015649 | Pentostatin |
| D011878 | Radiotherapy |
| D000069585 | Filgrastim |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003070 | Coformycin |
| D005573 | Formycins |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D013812 | Therapeutics |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
|
| OG001 | Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | 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. |
|
|
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.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|