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
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|ClinicalTrials.gov Identifier: NCT02989701|
Recruitment Status : Completed
First Posted : December 12, 2016
Last Update Posted : January 25, 2018
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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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Experimental: Single arm||
Dose escalation of Plerixafor for Hematopoietic stem cell mobilization in patients with Sickle Cell Disease
- 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.
- 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 ]
- Pre-apheresis peripheral CD34+ cell concentration >/= 5 cells/µL. [ Time Frame: 24 hours ]
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|Ages Eligible for Study:||18 Years to 35 Years (Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Diagnosis of sickle cell disease with genotype HbSS, HbS/ Beta 0 thalassemia, HbSD, or HbSO.
- Age 18-35 years.
- Receiving regularly-scheduled blood transfusions as part of existing medical care.
Adequate hematologic parameters including:
- White blood cell (WBC) count within the range of 2.5 - 25.0 x 109 /L
- Hemoglobin within the range of 5 - 11 g/dL
- Platelet count within the range of 150 - 700 x 109 /L
Adequate organ function and performance status
- Karnofsky performance status ≥70%
- Serum creatinine </= 1.5 times the upper limit of normal for age, and calculated creatinine clearance or GFR >/= 60 mL/min/1.73 m2.
- 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.
Patients who have uncontrolled illness including, but not limited to:
- Ongoing or active infection
- Emergency room admission or hospitalization for SCD-related reason in the past 30 days
- Major surgery in the past 30 days
- Medical/psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.
- Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics.
- Receipt of an investigational study drug or procedure within 90 days of study enrollment.
- Pregnant or breastfeeding.
- Known acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on prior biopsy.
- Known left ventricular ejection fraction <40% or known shortening fraction <25%.
- Known DLCO (corrected for hemoglobin), FEV1, and/or FVC < 50% of predicted.
- ALT > 2.5 X upper limit of normal or direct bilirubin > 2.0 mg/dL.
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 ClinicalTrials.gov identifier (NCT number): NCT02989701
|United States, Massachusetts|
|Boston Childrens Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Alessandra Biffi, MD||Boston Children's Hospital|
|Principal Investigator:||Erica Esrick, MD||Boston Children's Hospital|
|Responsible Party:||Alessandra Biffi, Director - Gene Therapy Program, Boston Children's Hospital|
|Other Study ID Numbers:||
|First Posted:||December 12, 2016 Key Record Dates|
|Last Update Posted:||January 25, 2018|
|Last Verified:||January 2018|
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn