Hemoglobinopathy (Disorder)Phase 2NCT04356469
TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children
A Phase 2 study testing Haploidentical Hematopoietic Cell Transplantation in people with Hemoglobinopathy (Disorder) and Severe Aplastic Anemia, run by Johns Hopkins All Children's Hospital at 1 site in United States.
Trial summary
This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. Read more about this study
- Who is it for?
- Ages 0 to 21 years
- Conditions the study is for
- Hemoglobinopathy (Disorder), Severe Aplastic Anemia, Bone Marrow Failure Syndrome
- What is being tested?
- Haploidentical Hematopoietic Cell Transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jul 2020to 30 Jun 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Severe sickle cell disease (HbSS, HbSC, HbSB0, HbSB+, HbSD, HbSE) with at least one of the following criteria:
- Cerebrovascular accident lasting longer than 24 hours
- Impaired neuropsychological function with abnormal brain MRI/MRA
- Patients with frequent (≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes
- Recurrent (≥ 3 in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy
- Any combination of ≥ 3 acute chest syndrome episodes and vaso-occlusive pain episodes yearly for 3 years and have failed treatment with hydroxyurea (HU) (at least 6 months on maximum tolerated dose) or who are intolerant to HU therapy
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- Thalassemia major with at least one of the following criteria:
- Transfusion dependency defined as receiving 8 or more transfusions per year
- Thalassemia diagnosis documented by clinical assessment, laboratory evidence with microcytic anemia and absence of HbA (< 10%) on electrophoresis and or confirmation by DNA analysis of alpha and beta gene loci
- Genotypically proven thalassemia major for children < 2 years of age even in the absence of transfusion dependency
- Lucarelli class 1 or 2 risk status (i.e. with only 0-2 of the following factors: hepatomegaly, portal fibrosis, or poor response to chelation therapy)
- Bone marrow failure syndromes and autoimmune cytopenias:
- Severe Aplastic Anemia refractory to immunosuppressive therapy
- Diamond Blackfan Anemia refractory to conventional therapy
- Inherited Bone Marrow Failure Syndromes such as Fanconi anemia and Shwachman-Diamond syndrome with progressive marrow failure (without cytogenetic evidence of MDS/AML)
- Severe Congenital Neutropenia
- Congenital Amegakaryocytic Thrombocytopenia
- Glanzmann Thrombasthenia
- Autoimmune Cytopenias refractory to conventional treatment (including Pure red cell aplasia, Evan's syndrome, Immune thrombocytopenia, autoimmune hemolytic anemia)
- Other marrow failure disorders not otherwise specified
- Patient has a suitable genotypic identical match of 5/10. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1.
- Patients must have adequate organ function measured by:
- Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%
- Pulmonary: asymptomatic or if symptomatic DLCO ≥ 40% of predicted (corrected for hemoglobin) or pulse oximetry ≥ 92% on room air if the patient is unable to perform pulmonary function testing.
- Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m2.
- Hepatic: Serum conjugated (direct) bilirubin < 2.0 x ULN for age as per local laboratory unless attributable to Gilbert's syndrome; AST and ALT < 5.0 x ULN for age as per local laboratory. Patients with hyperbilirubinemia as a consequence of hyperhemolysis, or a profound change in serum hemoglobin post blood transfusion, are not excluded.
- Karnofsky or Lansky (age-dependent) performance score ≥ 50
- Signed written informed consent
Who cannot join
- Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donors are not excluded.
- Pregnant or breastfeeding females.
- Patient has HIV or uncontrolled fungal, bacterial or viral infections.
- Patient has received prior solid organ transplant.
- Patient has active GVHD (> grade II) or chronic extensive GVHD due to a previous allograft at the time of inclusion.
- For patients with hemoglobinopathy, liver biopsy is necessary if the patient has received chronic transfusions for over a year and has two ferritin levels of ≥ 1000 ng/ml. Patients with cirrhosis, extensive bridging hepatic fibrosis, or active hepatitis are excluded from enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Ian Snyder, isnyder5@jhmi.edu
Deepak Chellapandian, MD
About this study
Official title: Study of TCR Alpha Beta T-Cell and CD19 B-Cell Depletion for Hematopoietic Cell Transplantation From Haploidentical Donors in the Treatment of Non-Malignant Hematological Disorders in Children
This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.
- Being tested
- Haploidentical Hematopoietic Cell Transplantation
- Medical subject headings
- Hemoglobinopathies, Anemia, Aplastic, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haploidentical Hematopoietic Cell TransplantationBiological
TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation
| Study group | Role | What they receive |
|---|---|---|
| TCR alpha beta T cell depletion | Experimental | The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol Receives: Biological: Haploidentical Hematopoietic Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of successful donor engraftment
The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (< 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), > 95%=full donor chimerism.
Measured: Day 100 after transplantation
Secondary outcomes (7)
Overall survival and Event-free survival
Overall survival is defined as the time of enrollment to death from any cause or last follow up.
Event-free survival is defined as the time of enrollment to death, primary or secondary graft failure, graft failure necessitating a second HCT procedure, DLI or stem cell boost given for treatment of falling chimerism, or disease recurrence
Measured: Up to 2 years post transplant
Kinetics of neutrophil and platelet engraftment
Neutrophil engraftment defined as absolute neutrophil count ≥500/μL for 3 consecutive measurements on different days and platelet engraftment defined as sustained platelet count >20,000/μL and >50,000//μL with no platelet transfusions in the preceding seven days.
Measured: Up to 42 days post transplant
Transplant-related mortality
Rate of transplant-related mortality
Measured: Up to 100 days post transplant
Acute grade II-IV GvHD and Chronic GvHD
Incidence and severity of acute and chronic graft versus host disease
Measured: Up to 2 years post transplant
Primary and secondary graft failure
Rates of primary and secondary graft failure
Measured: Up to 2 years post transplant
Transplant-related complications and infections
Frequency of transplant-related complications and rate of infections following transplantation
Measured: Up to 2 years post transplant
Cellular and Immunological reconstitution by laboratory evaluations
The recovery of different lymphocyte subpopulation (CD3+; CD4+; CD8+; CD3+CD45RA+and CD45RO; TCR alpha beta; TCR gamma delta; CD19+)
Measured: Up to 2 years post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start22 Jul 2020
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemoglobinopathy (Disorder)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins All Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Deepak Chellapandian, MD, Principal investigator, Johns Hopkins All Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04356469
- Sponsor's protocol ID
- HAP-HEM
- Other IDs
- IRB00249753
- Status last verified
- Jun 2026
- First submitted
- 19 Apr 2020
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No