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NCT02105766

Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure

Active, enrolled Phase 2 Results posted Last updated 11 March 2025
What this trial tests

Phase 2 trial testing Alemtuzumab in Sickle Cell Disease in 56 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
21 April 2014
Primary endpoint
31 December 2023
31 December 2027

Quick facts

Lead sponsorNational Heart, Lung, and Blood Institute (NHLBI)
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment56
Start date21 April 2014
Primary completion31 December 2023
Estimated completion31 December 2027
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Who can join

Adults 4 to 80, any sex, with Sickle Cell Disease or Thalassemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant Primary · 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

GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor10
Number of Participants With Donor Red Cells at 2 Years Post Stem Cell Transplant Primary · 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.

GroupValue95% CI
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant16
Mean CD34+ Cell Dose Secondary · Day 0 up to Day 1

Mean CD34+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected

GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor19.08± 8.38
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant14.98± 5.95
Mean CD3+ Cell Dose Secondary · Day 0 up to Day 1

Mean CD3+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected

GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor3.12± 1.37
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant3.29± 1.57
Median Percent of Donor T-cells and Myeloid Chimerism Secondary · 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.

myeloid chimerism D30
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor10080 – 100
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant99.568 – 100
myeloid chimerism D60
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor10054 – 100
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant10029 – 100
myeloid chimerism D100
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor10042 – 100
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant10016 – 100
myeloid chimerism Year 1
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor10047 – 100
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant10054 – 100
myeloid chimerism Year 2
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor10044 – 100
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant9945 – 100
donor T-cells D30
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor65.516 – 94
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant251 – 85
donor T-cells D60
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor392 – 86
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant231 – 100
donor T-cells D100
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor340 – 91
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant22.52 – 96
Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV Secondary · 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. Gra

Grade I
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor0
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant0
Grade II
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor0
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant1
Grade III
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor1
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant0
Grade IV
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor0
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant0
Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) Secondary · 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.

Moderate
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor0
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant0
Severe
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor0
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant0
Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant Secondary · 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.

graft failure
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor1
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant0
red cell aplasia
GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor0
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant2
Number of Participants That Experienced Regimen Failure Secondary · 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.

GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor2
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant2
Number of Participants That Experienced Transplant-related Mortality Secondary · 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).

GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor0
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant0
Percentage of Participant With Disease-free Survival Following Stem Cell Transplant Secondary · 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.

GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor9
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant16
Percentage of Participant Overall Survival Following Stem Cell Transplant Secondary · 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.

GroupValue95% CI
Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor10
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant17

Adverse events — posted to ClinicalTrials.gov

Time frame: 5 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Female Participants With SCD or Beta-thalassemia Receiving Stem Cell Transplant With Male Donor
Serious: 9/11 (82%)
Deaths: 1/11
Participants With Pre-existing Antibodies and SCD or Beta-thalassemia Receiving Stem Cell Transplant
Serious: 13/18 (72%)
Deaths: 1/18
Human Leukocyte Antigens (HLA) Matched Related Stem Cell Donor
Serious: 2/27 (7%)
Deaths: 0/27

Serious adverse events (53 terms)

ReactionSystemFemale Participants With S…Participants With Pre-exis…Human Leukocyte Antigens (…
PainMusculoskeletal and connective tissue disorders
BacteremiaInfections and infestations
Cytomegalovirus (CMV) ReactivationInfections and infestations
DiarrheaGastrointestinal disorders
Lung infectionInfections and infestations
Vaso-occlusive pain crisisMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Avascular necrosisMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Enterocolitis infectiousInfections and infestations
FeverGeneral disorders
Skin infectionInfections and infestations
HypocalcemiaInvestigations
HypomagnesemiaInvestigations
AnorexiaMetabolism and nutrition disorders
Clostridioides difficile colitisInfections and infestations
Catheter related infectionInfections and infestations
DyspneaRespiratory, thoracic and mediastinal disorders
Epstein-Barr virus (EBV) viremiaInfections and infestations
Micro Papillary Thyroid CarcinomaEndocrine disorders
FatigueGeneral disorders
GastroparesisGastrointestinal disorders
Herpes simplex reactivationInfections and infestations
HyperkalemiaMetabolism and nutrition disorders
HyperthyroidismEndocrine disorders
Other adverse events (74 terms — click to expand)

ReactionSystemFemale Participants With S…Participants With Pre-exis…Human Leukocyte Antigens (…
Lymphocyte count decreasedBlood and lymphatic system disorders
Neutrophil count decreasedBlood and lymphatic system disorders
Platelet count decreasedBlood and lymphatic system disorders
PainMusculoskeletal and connective tissue disorders
AnemiaBlood and lymphatic system disorders
White blood cell decreasedBlood and lymphatic system disorders
HypertensionCardiac disorders
Cytomegalovirus (CMV) ReactivationInfections and infestations
Febrile neutropeniaBlood and lymphatic system disorders
DiarrheaGastrointestinal disorders
Lung infectionInfections and infestations
InsomniaPsychiatric disorders
Mucositis oralGastrointestinal disorders
Non-cardiac chest painMusculoskeletal and connective tissue disorders
Catheter related infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
Acute GVHDBlood and lymphatic system disorders
CD4 lymphocytes decreasedBlood and lymphatic system disorders
HemolysisBlood and lymphatic system disorders
Sinus tachycardiaCardiac disorders
CataractEye disorders
Eye painEye disorders
HemianopsiaEye disorders
Anal fistulaGastrointestinal disorders
ColitisGastrointestinal disorders
ConstipationGastrointestinal disorders
GastroparesisGastrointestinal disorders
NauseaGastrointestinal disorders
ToothacheGastrointestinal disorders
Upper gastrointestinal hemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
AgitationGeneral disorders
ChillsGeneral disorders
Infusion related reactionGeneral disorders
NauseaGeneral disorders
Cytokine release syndromeImmune system disorders
HypogammaglobulinemiaImmune system disorders
Anorectal infectionInfections and infestations
Endocarditis infectiveInfections and infestations

Most-reported serious reactions: Pain, Bacteremia, Cytomegalovirus (CMV) Reactivation, Diarrhea, Lung infection, Vaso-occlusive pain crisis, Arthralgia, Avascular necrosis.

Data from ClinicalTrials.gov NCT02105766 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. At least 20% donor myeloid chimerism is necessary to reverse the sickle phenotype after allogeneic HSCT.
    Fitzhugh CD, Cordes S, Taylor T, Coles W, et al · · 2017 · cited 127× · PMID 28887325 · DOI 10.1182/blood-2017-03-772392
  2. The hypoxia-adenosine link during inflammation.
    Bowser JL, Lee JW, Yuan X, Eltzschig HK. · · 2017 · cited 90× · PMID 28798196 · DOI 10.1152/japplphysiol.00101.2017
  3. Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells.
    Cromer MK, Camarena J, Martin RM, Lesch BJ, et al · · 2021 · cited 75× · PMID 33737751 · DOI 10.1038/s41591-021-01284-y
  4. Stem cell transplantation in sickle cell disease: therapeutic potential and challenges faced.
    Leonard A, Tisdale JF. · · 2018 · cited 46× · PMID 29883237 · DOI 10.1080/17474086.2018.1486703
  5. Increased incidence of hematologic malignancies in SCD after HCT in adults with graft failure and mixed chimerism.
    Lawal RA, Mukherjee D, Limerick EM, Coles W, et al · · 2022 · cited 32× · PMID 36044658 · DOI 10.1182/blood.2022017960
  6. Novel Therapeutic Advances in β-Thalassemia.
    Makis A, Voskaridou E, Papassotiriou I, Hatzimichael E. · · 2021 · cited 28× · PMID 34207028 · DOI 10.3390/biology10060546
  7. Immunohaematological complications in patients with sickle cell disease after haemopoietic progenitor cell transplantation: a prospective, single-centre, observational study.
    Allen ES, Srivastava K, Hsieh MM, Fitzhugh CD, et al · · 2017 · cited 27× · PMID 29100558 · DOI 10.1016/s2352-3026(17)30196-5
  8. 2015 Clinical trials update in sickle cell anemia.
    Archer N, Galacteros F, Brugnara C. · · 2015 · cited 25× · PMID 26178236 · DOI 10.1002/ajh.24116

Verify or expand the search:

Other trials of Alemtuzumab

Trials testing the same drug.

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Currently open trials in the same condition.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02105766.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing