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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Plerixafor


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Cohort - Plerixafor<br>Plerixafor at a single dose of 240 microgram/kg | Drug: Plerixafor<br>* Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg<br>* Other names: Mozobil®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plerixafor, Leukapheresis, Mobilization, Stem Cells, Sickle Cell Disease