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Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

Primary Purpose

Sickle Cell Disease, Thalassemia Major

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
CliniMACS
Sponsored by
Timothy Olson
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's Hospital of PhiladelphiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Sickle Cell Disease

Beta Thalassemias Major

Arm Description

Patients with Sickle Cell Disease (SCD) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.

Patients with Beta Thalassemias Major (BTM) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.

Outcomes

Primary Outcome Measures

Rate of graft failure
Time to neutrophil engraftment
Incidence of acute graft vs. host disease (GVHD)
Incidence of chronic graft vs. host disease (GVHD)

Secondary Outcome Measures

Number of deaths due to treatment
Probability of event-free survival (EFS)
Probability of overall survival (OS)
Incidence of viral reactivation and symptomatic viral infection

Full Information

First Posted
August 19, 2020
Last Updated
January 17, 2023
Sponsor
Timothy Olson
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1. Study Identification

Unique Protocol Identification Number
NCT04523376
Brief Title
Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 14, 2020 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Timothy Olson

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Thalassemia Major

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sickle Cell Disease
Arm Type
Experimental
Arm Description
Patients with Sickle Cell Disease (SCD) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.
Arm Title
Beta Thalassemias Major
Arm Type
Experimental
Arm Description
Patients with Beta Thalassemias Major (BTM) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.
Intervention Type
Device
Intervention Name(s)
CliniMACS
Intervention Description
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
Primary Outcome Measure Information:
Title
Rate of graft failure
Time Frame
Up to 1year post-transplantation
Title
Time to neutrophil engraftment
Time Frame
Up to 60 days post-transplantation
Title
Incidence of acute graft vs. host disease (GVHD)
Time Frame
Up to 100 days post-transplantation
Title
Incidence of chronic graft vs. host disease (GVHD)
Time Frame
Up to three years post-transplantation
Secondary Outcome Measure Information:
Title
Number of deaths due to treatment
Time Frame
Up to 100 days post-transplantation
Title
Probability of event-free survival (EFS)
Time Frame
Up to 1 year post-transplantation
Title
Probability of overall survival (OS)
Time Frame
Up to 1 year post-transplantation
Title
Incidence of viral reactivation and symptomatic viral infection
Time Frame
Up to 1 year post-transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Barb McGlynn, RN, BSN
Phone
215-590-1303
Email
MCGLYNN@chop.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Timothy Olson, MD, PhD
Phone
267-426-5516
Email
olsont@chop.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy Olson, MD, PhD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barb McGlynn, RN, BSN
Phone
215-590-1303
Email
MCGLYNN@chop.edu
First Name & Middle Initial & Last Name & Degree
Timothy Olson, MD, PhD
Phone
267-426-5516
Email
OLSONT@chop.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

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