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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04523376
Other study ID # 19-017141
Secondary ID
Status Active, not recruiting
Phase N/A
First received
Last updated
Start date May 14, 2020
Est. completion date December 1, 2024

Study information

Verified date April 2024
Source Children's Hospital of Philadelphia
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a single arm pilot study of peripheral stem cell transplantation (PSCT) with ex vivo t-cell receptor alpha beta+(TCRαβ+) T cell and cluster of differentiation 19+ beta (CD19+ B) cell depletion of unrelated donor (URD) grafts using the CliniMACS device in patients with sickle cell disease (SCD) and beta thalassemia major (BTM).


Description:

This is a single arm pilot study of peripheral stem cell transplantation (PSCT) with ex vivo TCRαβ+ T cell and CD19+ B cell depletion of URD grafts using the CliniMACS device in patients with SCD and BTM. Apart from CliniMACS-based cell processing, PSCT will be performed according to current standards of care in the Children's Hospital of Philadelphia (CHOP) Cell Therapy and Transplant Section, including the use of a standard chemotherapy conditioning regimen and standard follow-up laboratory assessments. The study will determine efficacy of this strategy in terms of engraftment, rates of acute and chronic Graft versus Host Disease (GvHD), and one-year overall and event-free survival.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 20
Est. completion date December 1, 2024
Est. primary completion date December 1, 2024
Accepts healthy volunteers No
Gender All
Age group 2 Years to 25 Years
Eligibility Inclusion criteria Severe Sickle Cell Disease - Genotype: Hemoglobin SS, Hemoglobin SC, Hemoglobin SD, SOArab, or Hemoglobin SBeta thalassemia - Must have at least one of the following disease manifestations - Clinically symptomatic neurologic event (stroke) or any neurologic deficit lasting greater than 24 hours at any time prior to enrollment - History of two or more episodes of vaso-occlusive events (VOE) per year in the 2 years preceding enrolment. Patients must be refractory to hydroxyurea, defined as developing VOE despite receiving hydroxyurea for at least 6 months. Patients who are intolerant of hydroxyurea may also be enrolled. Vaso-occlusive events include: - Acute chest syndrome - Pain episodes requiring intravenous pain management and/or hospitalization - Priapism - Splenic sequestration (defined as a 2 g/dL drop in hemoglobin in the setting of an acutely enlarging spleen. This will be determined as part of clinical care and prior to the research) - Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving = 8 RBC transfusions in the year preceding enrollment to prevent sickle cell-related complications of any kind per treating hematologist's judgment. Beta Thalassemia Major - Genotype: Confirmed Beta Thalassemia genotype by molecular genetic testing (May include E/Beta0 and Beta0/Beta+ genotypes) - Must meet clinical diagnosis of transfusion-dependent thalassemia, defined as need for = 8 RBC transfusions per year in the two years preceding study enrollment. Exclusion criteria - Patients who do not meet disease, organ or infectious criteria. - Previous Hematopoietic stem cell transplant (HSCT) - Patients with no suitable unrelated donor available. Patients with suitable fully matched related donor are also not eligible. - Pregnant females. All females of childbearing potential must have negative pregnancy test. - Participation in a clinical trial in which the patient receives an investigational drug must be discontinued prior to the time of initiation of transplant therapy. Specifically transplant chemotherapy should not begin until at least 3 half-lives after last use of the investigational drug. - Severe RBC alloimmunization, defined as inability to receive packed RBC transfusion therapy due to anti-RBC antibodies. Patients with high titer anti-donor human leukocyte antigen (HLA) antibodies detected on screening may be enrolled if they are willing to undergo HLA antibody desensitization therapy.

Study Design


Intervention

Device:
CliniMACS
Peripheral blood stem cells from closely matched unrelated donors will be processed using the CliniMACS device to remove TCRalpha/beta T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique

Locations

Country Name City State
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Timothy Olson

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Rate of graft failure Number of patients with primary graft failure (defined as no evidence of neutrophil engraftment by day +30 after stem cell infusion) and secondary graft failure (defined as ANC <500 for at least 7-10 days after initial engraftment occurs in the absence of known infection or drug-mediated suppression, and confirmed by hypocellular bone marrow biopsy and/or total donor chimerism percentage from blood or bone marrow < 10 percent) Up to 1year post-transplantation
Primary Time to neutrophil engraftment Number of days to neutrophil engraftment (first day of ANC >500/µl for the first of 3 consecutive days) Up to 60 days post-transplantation
Primary Incidence of acute graft vs. host disease (GVHD) Number of patients with acute GvHD (graded according to the current guidelines for reporting by the Center for International Bone Marrow Transplant Registry) Up to 100 days post-transplantation
Primary Incidence of chronic graft vs. host disease (GVHD) Number of patients with Grade II-IV acute GVHD, Severe Grade III-IV acute GVHD, and Chronic Extensive GVHD Up to three years post-transplantation
Secondary Number of deaths due to treatment Number of deaths due to treatment Up to 100 days post-transplantation
Secondary Probability of event-free survival (EFS) Number of patients without complications or events Up to 1 year post-transplantation
Secondary Probability of overall survival (OS) Number of patients with the following survival outcome: one-year overall survival (OS) 1 year post-transplantation
Secondary Incidence of viral reactivation and symptomatic viral infection Number of patients experiencing viral reactivation requiring therapy and symptomatic viral infections, including CMV, adenovirus, and EBV Up to 1 year post-transplantation
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