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Pilot and Feasibility Trial of Plerixafor for Hematopoietic Stem Cell (HSC) Mobilization in Patients With Sickle Cell Disease Pilot and Feasibility Trial of Plerixafor for Hematopoietic Stem Cell (HSC) Mobilization in Patients With Sickle Cell Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02989701
Recruitment Status : Completed
First Posted : December 12, 2016
Last Update Posted : January 25, 2018
Information provided by (Responsible Party):
Alessandra Biffi, Boston Children's Hospital

Brief Summary:

Sickle cell disease (SCD) is one of the most common genetic diseases in the world. In North America, an estimated 2600 babies are born with SCD each year1, and approximately 70,000 to 100,000 individuals of all ages are affected in the United States2. The clinical manifestations of SCD include acute events, such as recurrent debilitating painful crises, as well as life-threatening pulmonary, cardiovascular, renal, and neurologic complications. The only established curative treatment for SCD patients is allogeneic hematopoietic stem cell transplant (HSCT). Unfortunately, access to this intervention is limited by availability of suitable matched donors, and HSCT is associated with significant morbidity and mortality. For patients who cannot undergo HSCT, treatment of SCD has been limited to one FDA-approved medication, hydroxyurea, and supportive symptomatic care. After decades with very few novel therapeutic options for SCD patients, autologous cell-based genetic therapies, including lentiviral-based gene therapy as well as gene editing, now offer the possibility of innovative curative approaches for patients lacking a matched donor for hematopoietic stem cell transplantation.

Gene therapy for sickle cell disease is increasingly promising, and there are currently open clinical trials at several centers that employ a gene addition strategy.

Options for autologous HSC collection include bone marrow harvest or peripheral blood HSC mobilization. Bone marrow (BM) harvest is an invasive procedure requiring anesthesia, which is associated with sickle cell-related morbidities, and may not achieve goal CD34+ cell dose, necessitating repeated procedures scheduled over multiple months. In most gene therapy trials, HSCs are obtained through peripheral collection after mobilization with granulocyte colony-stimulating factor (G-CSF) followed by peripheral blood (PB) apheresis. However, this approach is contraindicated in SCD because G-CSF has been reported to cause severe adverse effects in sickle cell patients. Even with doses sometimes smaller than standard, G-CSF has been shown to result in vaso-occlusive crises, severe acute chest syndrome, and in one report, massive splenomegaly and death. Alternative options for mobilization are needed.

Plerixafor has been compared to G-CSF in a sickle cell mouse model, and results showed effective mobilization of HSC subsets, without neutrophil or endothelial activation, and with lower total WBC and neutrophil counts compared to G-CSF-treated mice. Plerixafor use has not yet been documented in sickle cell patients. One other trial is currently open to test plerixafor in SCD patients (NCT02193191) but no results have yet been reported. Based on pre-clinical data, the mechanism of action of plerixafor, as well strategies the investigator will employ to mitigate risk, the investigator anticipates that it will be well-tolerated in the SCD patient population.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Without Crisis Drug: Plerixafor Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot and Feasibility Trial of Plerixafor for Hematopoietic Stem Cell (HSC) Mobilization in Patients With Sickle Cell Disease
Study Start Date : January 2017
Actual Primary Completion Date : December 11, 2017
Actual Study Completion Date : December 11, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Plerixafor

Arm Intervention/treatment
Experimental: Single arm Drug: Plerixafor
Dose escalation of Plerixafor for Hematopoietic stem cell mobilization in patients with Sickle Cell Disease

Primary Outcome Measures :
  1. Safety will be assessed by monitoring for the occurrence of any described dose - limiting toxicities (DLTs) within 48 hours after dosing of plerixafor. [ Time Frame: 14 days post dose ]
    Occurrence of death, ICU admission, stroke, vasoocclusive pain crisis (VOC) requiring continuous or scheduled parenteral opioid analgesia, acute chest syndrome, acute CNS event, or any other disease-related adverse event of grade 3 or higher.

  2. Feasibility will be estimated by whether apheresis collection of a minimum of 0.5 X 106 CD34+ cells/kg is successful [ Time Frame: 14 days post dose ]

Secondary Outcome Measures :
  1. Pre-apheresis peripheral CD34+ cell concentration >/= 5 cells/µL. [ Time Frame: 24 hours ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of sickle cell disease with genotype HbSS, HbS/ Beta 0 thalassemia, HbSD, or HbSO.
  2. Age 18-35 years.
  3. Receiving regularly-scheduled blood transfusions as part of existing medical care.
  4. Adequate hematologic parameters including:

    1. White blood cell (WBC) count within the range of 2.5 - 25.0 x 109 /L
    2. Hemoglobin within the range of 5 - 11 g/dL
    3. Platelet count within the range of 150 - 700 x 109 /L
  5. Adequate organ function and performance status

    1. Karnofsky performance status ≥70%
    2. Serum creatinine </= 1.5 times the upper limit of normal for age, and calculated creatinine clearance or GFR >/= 60 mL/min/1.73 m2.
  6. Patients who are taking hydroxyurea are allowed to be included in this study. Hydroxyurea will be stopped 14 days prior to planned day of apheresis.

Exclusion Criteria:

  1. Patients who have uncontrolled illness including, but not limited to:

    1. Ongoing or active infection
    2. Emergency room admission or hospitalization for SCD-related reason in the past 30 days
    3. Major surgery in the past 30 days
    4. Medical/psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.
  2. Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics.
  3. Receipt of an investigational study drug or procedure within 90 days of study enrollment.
  4. Pregnant or breastfeeding.
  5. Known acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on prior biopsy.
  6. Known left ventricular ejection fraction <40% or known shortening fraction <25%.
  7. Known DLCO (corrected for hemoglobin), FEV1, and/or FVC < 50% of predicted.
  8. ALT > 2.5 X upper limit of normal or direct bilirubin > 2.0 mg/dL.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02989701

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United States, Massachusetts
Boston Childrens Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Alessandra Biffi
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Principal Investigator: Alessandra Biffi, MD Boston Children's Hospital
Principal Investigator: Erica Esrick, MD Boston Children's Hospital
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Responsible Party: Alessandra Biffi, Director - Gene Therapy Program, Boston Children's Hospital Identifier: NCT02989701    
Other Study ID Numbers: P00023325
First Posted: December 12, 2016    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018
Keywords provided by Alessandra Biffi, Boston Children's Hospital:
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hematologic Diseases
Genetic Diseases, Inborn
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents