We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Peripheral Blood Stem Cell Collection From Patients With Sickle Cell Disease (SCD) Using Plerixafor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04817345
Recruitment Status : Recruiting
First Posted : March 26, 2021
Last Update Posted : December 1, 2022
Sponsor:
Collaborator:
Doris Duke Charitable Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:

With recent advances in gene editing, gene therapy is becoming a viable curative treatment option for sickle cell disease. In order to do genetic manipulation, investigators need to collect hematopoietic stem cells from patients with sickle cell disease. In this study, investigators want to study the safety and feasibility of collecting peripheral blood stem cells from pediatric and young adult patients with sickle cell disease after administering plerixafor. Studying these peripheral blood stem cells will help in optimizing the yield of peripheral CD34+ cells from pediatric and young adult patients with sickle cell disease, which in turn will help to develop better gene therapies for these patients.

Primary Objectives

  • Determine the safety profile associated with administration of plerixafor in pediatric and young adult patients with sickle cell disease (SCD).
  • To estimate the number of CD34+ cells/kg of body weight that can be collected with peripheral apheresis after administration of plerixafor in pediatric and young adult patients with SCD.

Exploratory Objectives

  • To describe the kinetics of CD34+ cell mobilization in peripheral blood after - + cells obtained from pediatric and young adult patients with SCD.
  • To study the effect of hydroxyurea therapy on senescence in plerixafor-mobilized CD34+ cells obtained from pediatric and young adult patients with SCD.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Plerixafor Phase 2

Detailed Description:

Participants will be enrolled sequentially, and no two participants will undergo drug administration, mobilization or apheresis at the same time. A subsequent participant can only receive the study drug when the previous participant has been safely apheresed and discharged from the hospital. In the first stratum of the study only adult participants (18-25 years of age) will be enrolled. Once plerixafor and apheresis has been shown to be safe and acceptable in at least 5 adult participants, the study will enroll participants in the pediatric stratum. Pediatric stratum will not be activated until all the patients in the adult stratum have been evaluated and completed participation with acceptable results. In the pediatric stratum, older children (14 years old and above) will be enrolled before younger children (10-14 years old). After 10 participants, 14 years and older, have safely completed the study participation, younger children 10-14 years old will be allowed to participate.

Prophylactic red blood cell exchange or simple red cell transfusions will be given within 7 days prior to plerixafor administration to participants targeting HbS <30% to reduce the incidence of vaso-occlusive crisis and other events that may be associated with high hemoglobin S levels.Hydroxyurea treatment should be stopped 4 weeks before mobilization. Plerixafor administration and apheresis will be timed for participants already receiving chronic transfusion therapy such that the plerixafor administration and apheresis coincides with regularly timed transfusion.

Participants undergoing hematopoietic stem cell (HSC) mobilization will receive a daily-dose subcutaneous administration of plerixafor (Mozobil®) at 0.24 mg/kg on up to 2 consecutive days. Leukapheresis will start approximately 4 hours after each dose of plerixafor is given. This process lasts 4-10 hours.

Participants will be followed for 30 days after the last dose of plerixafor and then taken off study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Peripheral Blood Stem Cell Collection From Patients With Sickle Cell Disease (SCD) Using Plerixafor
Estimated Study Start Date : December 2022
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Plerixafor

Arm Intervention/treatment
Experimental: Plerixafor
Participants will receive a subcutaneous dose of 0.24 mg/kg of plerixafor once daily (Q24hr) x 2 days.
Drug: Plerixafor
Subcutaneous
Other Name: Mozobil ™




Primary Outcome Measures :
  1. Number of participants with sufficient collection of hematopoietic stem cells (HSCs) without serious adverse events. [ Time Frame: 2 days ]
    Sufficient collection of HSCs from peripheral blood after plerixafor mobilization without serious adverse events (SAEs)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   10 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with severe SCD who are 10-25 years old and are willing to donate autologous HSCs for advancing future gene therapy for SCD. Parents/legal guardians of participants must be able and willing to consent for their participation in this study. Severe SCD, for the purpose of this study, will be defined as patients who are receiving chronic transfusion therapy due to SCD related complications. The need for undergoing chronic transfusion therapy must be determined by the primary hematologist. Some patients may continue to receive hydroxyurea in addition to and simultaneously with blood transfusion therapy. Such patients are eligible for inclusion on the study if they hold hydroxyurea for at least 4 weeks. The ability to hold hydroxyurea (or not) with ongoing chronic transfusion therapy will be made by the primary hematologist as well. All genotypes of SCD will be eligible.
  • Adequate renal function: serum/plasma creatinine < 1.5 mg/dL and creatinine clearance > 50 mL/min (as calculated by the Crockcroft-Gault formula).
  • Adequate liver function: direct bilirubin < 2.5 times the upper limit of normal range, AST and ALT < 5 times the upper limit of normal range.
  • Blood counts: WBC > 3,000/mm^3, granulocytes > 1,000/mm^3, hemoglobin > 7.0 g/dL, platelets > 150,000/mm^3.
  • Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, have had a hysterectomy, be post-menopausal.
  • Negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1/II.
  • Participants should either have a central line in place or be able to undergo apheresis without the necessity of the insertion of a central venous catheter
  • Participants of childbearing potential should agree to use of an effective form of contraception during treatment and for at least 1 week after the last dose of plerixafor.
  • ECOG performance status/Karnofsky score/Lansky score >80.

Exclusion Criteria:

  • Pregnancy. Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, except those that have had a hysterectomy, or are post-menopausal.
  • Active viral, bacterial, fungal, or parasitic infection.
  • History of cancer, excluding squamous carcinoma of the skin and cervical carcinoma in situ.
  • Active and painful splenomegaly or splenomegaly (size greater than upper limit of normal) or splenic sequestration determined by ultrasound.
  • Previous history of splenomegaly or splenic sequestration, unless HbS level of <30% is documented within 48-72 hours of each plerixafor dose
  • Allergy to plerixafor.
  • Patients receiving hydroxyurea will not be included in the study. However, they may be included if the primary hematologist determines that hydroxyurea can be safely discontinued for at least 4 weeks prior to the plerixafor administration and apheresis. Generally, patients receiving chronic transfusion therapy can safely discontinue hydroxyurea therapy as there is unlikely to be any added benefit, but this will be determined by the primary treating hematologist.
  • Poor cardiac function, as defined by an ejection fraction < 40%.
  • History of clinically proven pulmonary hypertension.
  • Emergency room admission or hospitalization in the past 14 days prior to first dose of study drug.
  • Major surgery in the past 30 days prior to first dose of study drug.

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): NCT04817345


Contacts
Layout table for location contacts
Contact: Akshay Sharma, MBBS 866-278-5833 referralinfo@stjude.org

Locations
Layout table for location information
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Akshay Sharma, MBBS    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Akshay Sharma, MBBS         
Principal Investigator: Mitch Weiss, MD, PhD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Doris Duke Charitable Foundation
Investigators
Layout table for investigator information
Principal Investigator: Akshay Sharma, MBBS St. Jude Children's Research Hospital
Principal Investigator: Mitch Weiss, MD, PhD St. Jude Children's Research Hospital
Additional Information:
Layout table for additonal information
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT04817345    
Other Study ID Numbers: ASPIRES2
First Posted: March 26, 2021    Key Record Dates
Last Update Posted: December 1, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data will be made available at the time of article publication.
Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Jude Children's Research Hospital:
Plerixafor
Leukapheresis
Mobilization
Stem Cells
Sickle Cell Disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Plerixafor
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents