Graft vs Host Disease, Sickle Cell Disease, Stem Cell Transplantation, Thalassemia
Conditions
Keywords
Sickle Cell Disease, Allogeneic Hematopoietic Stem Cell Transplant, Pentostatin (Nipent), Cyclophosphamide, Alemtuzumab (Campath)
Brief summary
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: * Participants and donors will be screened with medical history, physical exam, blood test, tissue and blood typing, and bone marrow sampling. They will visit a social worker. * Donors: * may receive an intravenous (IV) tube in their groin vein. * will receive a drug injection daily for 5 or 6 days to move the blood stem cells from the bone marrow into general blood circulation. * will undergo apheresis: an IV is put into a vein in each arm. Blood is taken from one arm, a machine removes the white blood cells that contain blood stem cells, and the rest is returned through the other arm. * Participants: * may undergo red cell exchange procedure. * will remain in the hospital for about 30 days. * will receive a large IV line that can stay in their body from transplant through recovery. * will receive a dose of radiation, and transplant related drugs by mouth or IV. * will receive blood stem cells over 8 hours by IV. * will take neuropsychological tests and may complete questionnaires throughout the transplant process. * must stay near NIH for 4 months. They will visit the outpatient clinic weekly.
Detailed description
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.
Interventions
DRUGAlemtuzumab
Immunosuppressant
DRUGSirolimus
Immunosuppressant
DRUGCyclophosphamide
Immunosuppressant
DRUGPentostatin
Immunosuppressant
PROCEDURERadiotherapy
Immunosuppressant and myelosuppressant
DRUGFilgrastim
mobilize peripheral blood stem cells for apheresis collection
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
-INCLUSION CRITERIA- recipients (must fulfill one disease category in 1 and all of 2) 1. 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 * inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine 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 2cm below the costochondral margin Non-disease specific: -Age greater than or equal to 4 years -6/6 HLA matched family donor available * Ability to comprehend and willing to sign an informed consent * Negative beta-HCG, when applicable
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant | 1 year | 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 |
| Number of Participants With Donor Red Cells at 2 Years Post Stem Cell Transplant | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Day to Neutrophil Recovery | Up to Day 100 | 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. |
| Mean CD34+ Cell Dose | Day 0 up to Day 1 | Mean CD34+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected |
| Mean CD3+ Cell Dose | Day 0 up to Day 1 | Mean CD3+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected |
| Median Percent of Donor T-cells and Myeloid Chimerism | day 30, day 60 , day 100, 1 year and 2 year | 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. |
| Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Up to Day 100 | 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. |
| Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) | Day 100 up to 2 years | 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. |
| Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant | Up to 2 years | 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. |
| Number of Participants That Experienced Regimen Failure | Up to 2 years | 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. |
| Number of Participants That Experienced Transplant-related Mortality | Up to 2 years | 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). |
| Percentage of Participant With Disease-free Survival Following Stem Cell Transplant | Up to 2 years | 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. |
| Median Days to Platelet Recovery | Up to Day 120 | Median Days to Platelet Recovery. Platelet recovery is defined as count \>50 cells/uL and 7 days from the last platelet transfusion. |
| Percentage of Participant Overall Survival Following Stem Cell Transplant | Up to 2 years | Percentage of Participant Overall Survival up to year 2 following stem cell transplant. Overall survival is defined as being alive following stem cell transplant. |
| Median Days to Red Cell Recovery | Up to 2 years | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMatthew M Hsieh, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 11 |
| 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 | 18 |
| 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 | 27 |
| Total | 56 |
Baseline characteristics
| Characteristic | Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 3 Participants | 5 Participants | 8 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 15 Participants | 22 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 17 Participants | 25 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 16 Participants | 23 Participants | 49 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 11 participants | 18 participants | 27 participants | 56 participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 13 Participants | 19 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 11 | 1 / 18 | 0 / 27 |
| other Total, other adverse events | 11 / 11 | 18 / 18 | 0 / 27 |
| serious Total, serious adverse events | 9 / 11 | 13 / 18 | 2 / 27 |
Outcome results
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.
Time frame: 2 years
Population: Analysis is intended per protocol to include those participants from cohort 2 (patients with pre-existing antibody to donor red cells)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants With Donor Red Cells at 2 Years Post Stem Cell Transplant | 16 Participants |
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
Time frame: 1 year
Population: Analysis is intended per protocol for cohort 1 participants that received a stem cell transplant (female participants with male donors)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant | 10 Participants |
Secondary
Mean CD34+ Cell Dose
Mean CD34+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected
Time frame: Day 0 up to Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Mean CD34+ Cell Dose | 19.08 x10^6 cells/kg | Standard Deviation 8.38 |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Mean CD34+ Cell Dose | 14.98 x10^6 cells/kg | Standard Deviation 5.95 |
Secondary
Mean CD3+ Cell Dose
Mean CD3+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected
Time frame: Day 0 up to Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Mean CD3+ Cell Dose | 3.12 x10^8 cells/kg | Standard Deviation 1.37 |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Mean CD3+ Cell Dose | 3.29 x10^8 cells/kg | Standard Deviation 1.57 |
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.
Time frame: Up to Day 120
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Days to Platelet Recovery | 21.5 days |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Days to Platelet Recovery | 22.5 days |
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.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Days to Red Cell Recovery | 22 days |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Days to Red Cell Recovery | 19 days |
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.
Time frame: Up to Day 100
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Day to Neutrophil Recovery | 22 days |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Day to Neutrophil Recovery | 20.5 days |
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.
Time frame: day 30, day 60 , day 100, 1 year and 2 year
Population: Analysis includes those participants who have sustained engraftment or did not experience graft failure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism D100 | 100 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells D30 | 65.5 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism D60 | 100 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells D60 | 39 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism Year 1 | 100 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells D100 | 34 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells Year 1 | 70 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism D30 | 100 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells Year 2 | 74.5 percentage of donor cells |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism Year 2 | 100 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells Year 2 | 62 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism D30 | 99.5 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism D60 | 100 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism D100 | 100 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism Year 1 | 100 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | myeloid chimerism Year 2 | 99 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells D30 | 25 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells D60 | 23 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells Year 1 | 43 percentage of donor cells |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Median Percent of Donor T-cells and Myeloid Chimerism | donor T-cells D100 | 22.5 percentage of donor cells |
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.
Time frame: Up to 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant | graft failure | 1 Participants |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant | red cell aplasia | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant | graft failure | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant | red cell aplasia | 2 Participants |
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.
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants That Experienced Regimen Failure | 2 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants That Experienced Regimen Failure | 2 Participants |
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).
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants That Experienced Transplant-related Mortality | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants That Experienced Transplant-related Mortality | 0 Participants |
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.
Time frame: Up to Day 100
Population: Analysis includes those participants who have sustained engraftment or did not experience graft failure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade I | 0 Participants |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade II | 0 Participants |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade III | 1 Participants |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade IV | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade IV | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade I | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade III | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV | Grade II | 1 Participants |
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.
Time frame: Day 100 up to 2 years
Population: Analysis includes those participants who have sustained engraftment or did not experience graft failure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) | Moderate | 0 Participants |
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) | Severe | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) | Moderate | 0 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) | Severe | 0 Participants |
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.
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Percentage of Participant Overall Survival Following Stem Cell Transplant | 10 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Percentage of Participant Overall Survival Following Stem Cell Transplant | 17 Participants |
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.
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor | Percentage of Participant With Disease-free Survival Following Stem Cell Transplant | 9 Participants |
| Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant | Percentage of Participant With Disease-free Survival Following Stem Cell Transplant | 16 Participants |