Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

Sickle Cell Disease Clinical Trial

Official title:

Closely Matched Unrelated Donor Peripheral Blood Stem Cell Transplantation With TCRαβ+ T Cell and B Cell Depletion For Patients With Sickle Cell Disease and Thalassemia Major

Clinical Trial Details — Status: Active, not recruiting

Administrative data

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

Study information

• Verified date: June 2024
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• 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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• beta-Thalassemia
• Sickle Cell Disease
• Thalassemia
• Thalassemia Major

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