Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients

September 20, 2023 updated by: National Heart, Lung, and Blood Institute (NHLBI)

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

The constitution of blood relies upon hematopoietic stem cells (HSCs), which stay in the bone marrow and differentiate to all lineages of peripheral blood cells. HSC transplantation is the only curative option currently available for sickle cell disease (SCD) patients either via allogeneic HSC transplantation or HSC-targeted gene therapy. Granulocyte-colony stimulating factor (G-CSF)- mobilized HSCs are frequently utilized in the adult setting of HSC transplantation because of the faster hematologic recovery as compared to bone marrow. As an autologous HSC source for gene therapy, bone marrow harvest has been generally employed since G-CSF has been prohibitive in SCD patients due to granulocyte stimulation and the associated reports of vaso-occlusive crises, multi-organ failure, and death. However, when bone marrow harvest is used, the amounts of collected cells are limited and anesthesia is required. In order to obtain HSCs in large numbers without anesthesia, patients will undergo mobilization followed by large volume apheresis. Plerixafor is an alternative treatment for mobilization without direct stimulation to granulocytes, and it is theoretically applicable for SCD patients. The primary endpoint of this study is to obtain sufficient amounts of HSCs collected from the peripheral blood in SCD patients after plerixafor

mobilization with an acceptable safety profile. The harvested products will be stored as backup for patients undergoing gene therapy as well as allogeneic HSC transplantation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The constitution of blood relies upon hematopoietic stem cells (HSCs), which stay in the bone marrow and differentiate to all lineages of peripheral blood cells. HSC transplantation is the only curative option currently available for sickle cell disease (SCD) patients either via allogeneic HSC transplantation or HSC-targeted gene therapy. Granulocyte-colony stimulating factor (G-CSF)- mobilized HSCs are frequently utilized in the adult setting of HSC transplantation because of the faster hematologic recovery as compared to bone marrow. As an autologous HSC source for gene therapy, bone marrow harvest has been generally employed since G-CSF has been prohibitive in SCD patients due to granulocyte stimulation and the associated reports of vaso-occlusive crises, multi-organ failure, and death. However, when bone marrow harvest is used, the amounts of collected cells are limited and anesthesia is required. In order to obtain HSCs in large numbers without anesthesia, patients will undergo mobilization followed by large volume apheresis. Plerixafor is an alternative treatment for mobilization without direct stimulation to granulocytes, and it is theoretically applicable for SCD patients. The primary endpoint of this study is to obtain sufficient amounts of HSCs collected from the peripheral blood in SCD patients after plerixafor mobilization with an acceptable safety profile. The harvested products will be stored as backup for patients undergoing gene therapy as well as allogeneic HSC transplantation.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  • INCLUSION CRITERIA:
  • SCD patients who are 18 or older, and (a) planned to enroll in an active allogeneic HSCT study where back-up autologous HSCs are needed; OR (b) are eligible for an allogeneic HSCT study (i.e. have the same disease severity as group (a), but no active allogeneic HSCT study is available), and are willing to donate autologous HSCs for a future gene therapy, gene editing, or allogeneic HSCT study.
  • Adequate renal function: serum/plasma creatinine <1.5 mg/dL.
  • Adequate liver function: direct bilirubin and ALT <5 times the upper limit of normal range.
  • Blood counts: WBC >3,000/mm^3, granulocytes >1,000/mm^3, hemoglobin>7.0g/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, post-menopausal, or absence of a menses for over a year.
  • Meets NIH Department of Transfusion Medicine (DTM) eligibility criteria for blood component donation for in vitro research use (negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1).
  • Ability to give informed consent to participate in the protocol.
  • Female and male individuals of reproductive potential must agree to one of the contraceptive regimens stated above if sexually active

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, post-menopausal, or an absence of a menses for over a year.
  • 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) determined by ultrasound.
  • Allergy to plerixafor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Cohort - Plerixafor
Plerixafor at a single dose of 240 microgram/kg
Drug: Plerixafor
Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg
Other Names:
  • Mozobil®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Sufficient Collection of Hemopoietic Stem Cells (HSCs) Without Serious Adverse Events
Time Frame: 1 day
Sufficient collection of HSCs (target 2.0x106 CD34+ cells/kg) from the PB after plerixafor mobilization without serious adverse events (SAEs)
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborators

St. Jude Children's Research Hospital

Investigators

  • Principal Investigator: John F Tisdale, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2017

Primary Completion (Actual)

February 27, 2019

Study Completion (Actual)

February 27, 2019

Study Registration Dates

First Submitted

July 21, 2017

First Submitted That Met QC Criteria

July 21, 2017

First Posted (Actual)

July 24, 2017

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 20, 2023

Last Verified

June 6, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 170124
  • 17-H-0124

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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