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Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

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ClinicalTrials.gov Identifier: NCT04523376
Recruitment Status : Recruiting
First Posted : August 21, 2020
Last Update Posted : November 6, 2020
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

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).

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Thalassemia Major Device: CliniMACS Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 14, 2020
Estimated Primary Completion Date : July 1, 2024
Estimated Study Completion Date : July 1, 2024


Arm Intervention/treatment
Experimental: Sickle Cell Disease
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.
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

Experimental: Beta Thalassemis Major
Patients with Beta Thalassemis 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.
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




Primary Outcome Measures :
  1. Rate of graft failure [ Time Frame: Up to three years post-transplantation ]
  2. Time to neutrophil engraftment [ Time Frame: Up to 60 days post-transplantation ]
  3. Incidence of acute graft vs. host disease (GVHD) [ Time Frame: Up to 100 days post-transplantation ]
  4. Incidence of chronic graft vs. host disease (GVHD) [ Time Frame: Up to three years post-transplantation ]

Secondary Outcome Measures :
  1. Number of deaths due to treatment [ Time Frame: Up to 100 days post-transplantation ]
  2. Probability of event-free survival (EFS) [ Time Frame: Up to 1 year post-transplantation ]
  3. Probability of overall survival (OS) [ Time Frame: Up to 1 year post-transplantation ]
  4. Incidence of viral reactivation and symptomatic viral infection [ Time Frame: Up to 1 year post-transplantation ]


Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04523376


Contacts
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Contact: Barb McGlynn, RN, BSN 215-590-1303 MCGLYNN@email.chop.edu
Contact: Timothy Olson, MD, PhD 267-426-5516 olsont@email.chop.edu

Locations
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United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Barb McGlynn, RN, BSN    215-590-1303    MCGLYNN@email.chop.edu   
Contact: Timothy Olson, MD, PhD    267-426-5516    OLSONT@EMAIL.CHOP.EDU   
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
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Principal Investigator: Timothy Olson, MD, PhD Children's Hospital of Philadelphia
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Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT04523376    
Other Study ID Numbers: 19-017141
First Posted: August 21, 2020    Key Record Dates
Last Update Posted: November 6, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn