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

Primary Purpose

Sickle Cell Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Plerixafor
Sponsored by
National Heart, Lung, and Blood Institute (NHLBI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Sickle Cell Disease focused on measuring Plerixafor, Leukapheresis, Mobilization, Stem Cells, Sickle Cell Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • 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.

Sites / Locations

  • National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Cohort - Plerixafor

Arm Description

Plerixafor at a single dose of 240 microgram/kg

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 21, 2017
Last Updated
September 20, 2023
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborators
St. Jude Children's Research Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03226691
Brief Title
Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients
Official Title
Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients Using Plerixafor
Study Type
Interventional

2. Study Status

Record Verification Date
June 6, 2019
Overall Recruitment Status
Completed
Study Start Date
July 25, 2017 (Actual)
Primary Completion Date
February 27, 2019 (Actual)
Study Completion Date
February 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborators
St. Jude Children's Research Hospital

4. Oversight

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

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Plerixafor, Leukapheresis, Mobilization, Stem Cells, Sickle Cell Disease

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Cohort - Plerixafor
Arm Type
Experimental
Arm Description
Plerixafor at a single dose of 240 microgram/kg
Intervention Type
Drug
Intervention Name(s)
Plerixafor
Other Intervention Name(s)
Mozobil®
Intervention Description
Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg
Primary Outcome Measure Information:
Title
Number of Participants With Sufficient Collection of Hemopoietic Stem Cells (HSCs) Without Serious Adverse Events
Description
Sufficient collection of HSCs (target 2.0x106 CD34+ cells/kg) from the PB after plerixafor mobilization without serious adverse events (SAEs)
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John F Tisdale, M.D.
Organizational Affiliation
National Heart, Lung, and Blood Institute (NHLBI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33956057
Citation
Leonard A, Sharma A, Uchida N, Stroncek D, Panch SR, West K, Molloy E, Hughes TE, Hauffe S, Taylor T, Fitzhugh C, Hankins JS, Wilson M, Tsai SQ, Weiss MJ, Hsieh M, Tisdale JF. Disease severity impacts plerixafor-mobilized stem cell collection in patients with sickle cell disease. Blood Adv. 2021 May 11;5(9):2403-2411. doi: 10.1182/bloodadvances.2021004232.
Results Reference
derived
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-H-0124.html
Description
NIH Clinical Center Detailed Web Page

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

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