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Safety of Blood Stem Cell Mobilization With Plerixafor in Patients With Sickle Cell Disease (PISMO)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03664830
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE September 7, 2018
First Posted Date  ICMJE September 11, 2018
Last Update Posted Date September 26, 2019
Actual Study Start Date  ICMJE September 19, 2018
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
Toxicities [ Time Frame: 120 hours (5 days) from the last injection of plerixafor ]
Scored using the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 4.03
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
Stem cell mobilization feasibility [ Time Frame: 6 hours after the first injection of plerixafor. ]
Assessed by measuring the number of mobilized CD34+ cells/µL of peripheral blood
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of Blood Stem Cell Mobilization With Plerixafor in Patients With Sickle Cell Disease
Official Title  ICMJE A Pilot Study To Evaluate The Safety And Feasibility of Hematopoietic Progenitor Cell Mobilization With Plerixafor as Part of a Gene Therapy Strategy in Sickle Cell Disease
Brief Summary The objective of this study is to investigate if up to two injections of plerixafor represent a safe and effective strategy to mobilize adequate numbers of CD34+ hematopoietic stem progenitor cells (HSPC) for autologous hematopoietic cell transplantation (HCT) in sickle cell disease (SCD) patients
Detailed Description Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for sickle cell disease (SCD) patients but its use is significantly limited by the lack of compatible donors. Gene therapy using autologous hematopoietic stem cell (HSC) transplantation represents an alternative approach but requires the collection of significant numbers of cells. Severe adverse events have been observed in SCD patients after mobilization using the standard agent granulocyte colony-stimulating factor (G-CSF), and bone marrow harvesting is also associated with side effects. The use of a single administration of plerixafor has been suggested as an alternative mobilization strategy in SCD but may not mobilize sufficient number of HSC. In this study, our primary objective is to assess if up to two injections of plerixafor (starting dose level: 240 µg/kg/dose) are safe in SCD patients and can recruit enough blood stem cells needed for future gene therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Each SCD research participant will receive up to two subcutaneous injections of plerixafor (starting dose level: 240 µg/kg/dose)
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE Drug: Plerixafor
Up to two subcutaneous injections of plerixafor (starting dose level: 240 µg/kg/dose)
Study Arms  ICMJE Experimental: Plerixafor
Up to two subcutaneous injections of plerixafor (starting dose level: 240 µg/kg/dose)
Intervention: Drug: Plerixafor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 7, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Weight between 50 and 120 kg;
  • Karnofsky performance status (KPS) ≥70%;
  • Confirmed diagnosis of sickle cell disease with βS/βS or βS/β0 or βS/β+ genotype;
  • Must have had one or more of the following events in the 2 year period preceding enrollment:

    • History of ≥2 severe vaso-occlusive pain crises (VOC) (or at least two episodes in the year preceding the setting up of regular transfusion protocol). A severe VOC is defined as an episode of pain lasting more than 2 hours severe enough to require care at a medical facility.
    • History of ≥1 episodes of acute chest syndrome despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea)
    • Clinically significant neurological event (stroke) or any neurological deficit lasting 24 hours. A stroke is defined as a sudden neurological change lasting more than 24 hours that is accompanied by cerebral magnetic resonance imaging (MRI) changes.
    • Prior treatment with regular RBC transfusion therapy, defined as receiving ≥8 transfusions per year for >1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
    • Osteonecrosis of two or more joints;
    • Anti-erythrocyte alloimmunization (>2 antibodies);
    • Presence of sickle cell cardiomyopathy documented by Doppler echocardiography;
    • Presence of any significant cerebral abnormality such as stenosis or occlusions on magnetic resonance imaging (MRA)
  • Meet current eligibility requirements for donation for mobilization at the COH DAC;
  • Adequate renal function: defined as a creatinine estimated FDR (eGFR) of ≥60 ml/min;
  • Adequate liver function: defined by a serum conjugated (direct) bilirubin <2.5x upper limit of normal (ULN) for age; AST and ALT <5x ULN for age as per laboratory;
  • Adequate cardiac function: defined as left ventricular ejection fraction >50%;
  • Adequate hematologic parameters: WBC ≥2.5 x 10^9/L; platelet count ≥120 x10^9/L; hemoglobin >8 g/dL;
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry.

Exclusion Criteria:

  • Diagnosed with alpha thalassemia (two or more gene deletions or any α-globin structural variants);
  • Seropositivity for HIV-1/2 (Human Immunodeficiency Virus) or HTLV-1/2(Human T-Lymphotropic Virus);
  • Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to treatment. Participants with fever should await resolution of symptoms before starting the treatment;
  • Any clinically significant active infection which, in the opinion of the investigator, would require significant medical intervention;
  • Abnormal pulmonary function tests (adults with mild or moderate obstruction or restriction or diffusion defects are eligible, per Investigator discretion).
  • History of pulmonary hypertension, proven by cardiac catheterization;
  • History of malignancy or immunodeficiency disorder, (i.e., subjects with prior malignancy must be disease-free for 5 years), except curatively-treated basal cell carcinoma or cutaneous squamous cell carcinoma;
  • Participation in any study with an investigational agent or medical device within 90 days of screening;
  • Major surgery in the past 30 days;
  • Prior receipt of any gene transfer product;
  • Bone marrow harvest in the past year;
  • Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenesis;
  • Known hypersensitivity to plerixafor or any excipient contained in Mozobil;
  • G-CSF or plerixafor medication within 4 weeks of treatment;
  • Pregnant or nursing women;
  • Any condition or chronic physical, neurological, or mental illness, which in the opinion of the investigator, makes participation ill advised.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joseph Rosenthal, MD 626-256-4673 ext 88442 jrosenthal@coh.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03664830
Other Study ID Numbers  ICMJE 17426
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joseph Rosenthal, MD City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP