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

NCT ID: NCT03226691

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-25
• Study Completion Date: 2019-02-27

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.

Conditions

Sickle Cell Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Single Cohort - Plerixafor

Plerixafor at a single dose of 240 microgram/kg

Group Type: EXPERIMENTAL

Plerixafor

Intervention Type: DRUG

Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg

Interventions

Plerixafor

Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg

Intervention Type: DRUG

Other Intervention Names

Mozobil®

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Jude Children's Research Hospital

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John F Tisdale, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33956057 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-H-0124.html

NIH Clinical Center Detailed Web Page

Other Identifiers

17-H-0124

Identifier Type: -

Identifier Source: secondary_id

170124

Identifier Type: -

Identifier Source: org_study_id