- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04356469
TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children
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
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jade Hanson, MSN
- Phone Number: 7277676468
- Email: jade.hanson@jhmi.edu
Study Locations
-
-
Florida
-
Saint Petersburg, Florida, United States, 33701
- Recruiting
- Johns Hopkins All Children's Hospital
-
Contact:
- Ian Snyder
- Email: ISnyder5@jhmi.edu
-
Principal Investigator:
- Deepak Chellapandian, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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
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
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TCR alpha beta T cell depletion
The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol
|
TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of successful donor engraftment
Time Frame: Day 100 after transplantation
|
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.
|
Day 100 after transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival and Event-free survival
Time Frame: Up to 2 years post transplant
|
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 |
Up to 2 years post transplant
|
Transplant-related mortality
Time Frame: Up to 100 days post transplant
|
Rate of transplant-related mortality
|
Up to 100 days post transplant
|
Cellular and Immunological reconstitution by laboratory evaluations
Time Frame: Up to 2 years post transplant
|
The recovery of different lymphocyte subpopulation (CD3+; CD4+; CD8+; CD3+CD45RA+and CD45RO; TCR alpha beta; TCR gamma delta; CD19+)
|
Up to 2 years post transplant
|
Kinetics of neutrophil and platelet engraftment
Time Frame: Up to 42 days post transplant
|
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.
|
Up to 42 days post transplant
|
Acute grade II-IV GvHD and Chronic GvHD
Time Frame: Up to 2 years post transplant
|
Incidence and severity of acute and chronic graft versus host disease
|
Up to 2 years post transplant
|
Primary and secondary graft failure
Time Frame: Up to 2 years post transplant
|
Rates of primary and secondary graft failure
|
Up to 2 years post transplant
|
Transplant-related complications and infections
Time Frame: Up to 2 years post transplant
|
Frequency of transplant-related complications and rate of infections following transplantation
|
Up to 2 years post transplant
|
Collaborators and Investigators
Investigators
- Principal Investigator: Deepak Chellapandian, MD, Johns Hopkins All Children's Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HAP-HEM
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Severe Aplastic Anemia
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingRecurrent Severe Aplastic Anemia | Refractory Severe Aplastic AnemiaUnited States
-
University of UtahNovartisCompletedSevere Aplastic Anemia | Moderate Aplastic Anemia | Very Severe Aplastic AnemiaUnited States
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedSevere Aplastic Anemia, Refractory | Severe Aplastic Anemia, RelapseUnited States
-
Peking University People's HospitalRecruiting
-
Boston Children's HospitalNational Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health... and other collaboratorsRecruitingSevere Aplastic AnemiaUnited States
-
Shanghai General Hospital, Shanghai Jiao Tong University...Ruijin Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine and other collaboratorsCompleted
-
Navy General Hospital, BeijingPeking Union Medical College Hospital; Cancer Institute and Hospital, Chinese... and other collaboratorsUnknownSevere Aplastic AnemiaChina
-
Assistance Publique - Hôpitaux de ParisNot yet recruitingSevere Aplastic Anemia | Idiopathic Aplastic Anemia | Moderate Aplastic Anemia Requiring Transfusions
-
Jiangsu HengRui Medicine Co., Ltd.Recruiting
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedSevere Aplastic Anemia (SAA)United States
Clinical Trials on Haploidentical Hematopoietic Cell Transplantation
-
Johns Hopkins All Children's HospitalRecruitingMetabolic Disease | Primary Immune Deficiency DisordersUnited States
-
Institute of Hematology & Blood Diseases HospitalRecruiting
-
Samsung Medical CenterUnknownHaploidentical Stem Cell Transplantation and NK Cell Therapy in Patients With High-risk Solid TumorsSoft Tissue Sarcoma | Osteosarcoma | Ewing Sarcoma | Neuroblastoma | RhabdomyosarcomaKorea, Republic of
-
Andalusian Initiative for Advanced Therapies -...Iniciativa Andaluza en Terapias AvanzadasWithdrawnTransplant-Related Hematologic MalignancySpain
-
Azienda Ospedaliera San Giovanni BattistaUnknownMultiple MyelomaItaly
-
Roswell Park Cancer InstituteCelgeneWithdrawnRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | IDH2 Gene Mutation | Blasts Under 5 Percent of Peripheral Blood White Cells | Bone Marrow Blasts Decreased by 50 Percent or More Compared to Pretreatment LevelUnited States
-
University of ZurichRecruitingEnd Stage Renal DiseaseSwitzerland
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI)TerminatedAcute Lymphoblastic Leukemia | Mantle Cell Lymphoma | Non-Hodgkin Lymphoma | Myelodysplastic Syndrome | Plasma Cell Myeloma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Minimal Residual Disease | Therapy-Related Acute Myeloid Leukemia | Therapy-Related Myelodysplastic... and other conditionsUnited States
-
Wake Forest University Health SciencesCompletedLymphoma | Myelodysplastic Syndromes | Leukemia | Chronic Myeloproliferative Disorders | Multiple Myeloma and Plasma Cell NeoplasmUnited States
-
John MascarenhasNational Cancer Institute (NCI); Novartis; Incyte Corporation; Myeloproliferative...TerminatedPrimary Myelofibrosis | Post Essential Thrombocythemia Myelofibrosis | Post Polycythemia Vera MyelofibrosisUnited States, Canada, United Kingdom