Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Plerixafor
Intervention description: Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg
Intervention MeSH terms: Plerixafor
Phase: Phase 1
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Plerixafor; Leukapheresis; Mobilization; Stem Cells; Sickle Cell Disease

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.
    

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.