Escalation of Plerixafor for Mobilization of CD34+ Hematopoietic Progenitor Cells and Evaluation of Globin Gene Transfer in Patients With Sickle Cell Disease

Study Description

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Brief Summary:

The purpose of this research study is to test the safety and efficacy of a drug called Plerixafor. Plerixafor is approved by the US FDA for use in increasing blood stem cell counts before collection in cancer patients. It is not yet approved for patients with sickle cell disease. The investigators want to find out if Plerixafor can be used to increase cell counts in patients with sickle cell disease.

Condition or disease	Intervention/treatment	Phase
Sickle Cell Disease	Drug: Plerixafor	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	39 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Safety and Efficacy Trial of Escalation of Plerixafor for Mobilization of CD34+ Hematopoietic Progenitor Cells and Evaluation of Globin Gene Transfer in Patients With Sickle Cell Disease
Actual Study Start Date :	September 2014
Estimated Primary Completion Date :	July 2019
Estimated Study Completion Date :	July 2019

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Plerixafor; Patients will receive a single dose of subcutaneous plerixafor with peripheral blood studies at approximately 0-2 hours before, approximately 6-12 hours after, and approximately 20-48 hours after plerixafor administration, with leukapheresis in the last 3 patients on the protocol. Collected HPCs will be transferred to the MSKCC CTCEF to determine if the HPCs are amenable to transduction with a lentiviral vector encoding the normal ß- globin gene.

Drug: Plerixafor

Outcome Measures

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Primary Outcome Measures :

1. safety [ Time Frame: up to 30 days ]
   Safety is assessed using a dose limiting toxicity (DLT) endpoint. Definition of a DLT is the occurrence of any of the below events that meets the following criteria: The occurrence of a vasoocclusive crisis requiring hospitalization, acute chest syndrome, CNS acute event, or any other disease related ischemic-based adverse event (AE) should be considered as a DLT, if occurring in the 48 hours DLT observation period.
2. efficacy [ Time Frame: ≥ 30/ul at either 6-12 hours or 24-48 hours post plerixafor. ]
   Efficacy is defined as 100% of evaluable patients reaching a PB CD34 concentration ≥ 30/uL.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Patients must have confirmed and measurable Sickle Cell Disease, defined by SS or Sβ thalassemia confirmed by hemoglobin fractionation.
• ≥ 18 to 65 years of age
• Patient must have a ECOG performance status ≤2 or Karnofsky score > 70%

• Patients must have acceptable organ and marrow function as defined below:

  • WBC ≥ 3,000/μL
  • ANC ≥ 1,500/μL
  • platelets ≥150,000//μL
  • Hemoglobin ≥ 6 gm/dL
  • Calculated creatinine clearance ≥ 60ml/min * *Using the Cockcroft-gault equation [140 - Age(yrs)] [Weight(kg)] x 0.85 if Female 72 [Serum Creatinine (mg/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 and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

• Patients who are:

  • Receiving or received treatment with an investigational agent within 4 weeks prior to entering the study OR
  • have not recovered from adverse events due to agents administered more than 4 weeks earlier as determined by the treating physician.
• Patients with ALT(SGPT) > 2.5 X upper limit of normal
• Patients with a creatinine clearance of < 60 ml/min

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

  • Ongoing or active infection
  • Emergency room admission or hospitalization in the past 14 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.
• Female patients who are pregnant or breast-feeding
• Patients with active hepatitis B, hepatitis C, or HIV infection
• Patients with poor cardiac function as defined by an ejection fraction < 40% are excluded due to potential poor tolerance of the fluid shifts with leukapheresis (only for patients enrolled on second phase of protocol for Leukapheresis).

Contacts and Locations

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Contacts

Contact: Farid Boulad, MD	212- 639-6684
Contact: Susan Prockop, MD	212-639-6715

Locations

United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Farid Boulad, MD 212-639-6684
Contact: Susan Prockop, MD 212-639-6715
Principal Investigator: Farid Boulad, MD
Weill Cornell Medical College	Recruiting
New York, New York, United States, 10065
Contact: Tsiporah Shore, MD 212-746-2646
United States, North Carolina
Duke University	Not yet recruiting
Durham, North Carolina, United States, 27708
Contact: Jen-Tsan Chi, MD, PhD 919-668-4759
Principal Investigator: Jen-Tsan Chi, MD,PhD

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Sanofi

New York Blood Center

Weill Medical College of Cornell University

Duke University

Investigators

Principal Investigator:	Farid Boulad, MD	Memorial Sloan Kettering Cancer Center

More Information

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Additional Information:

Memorial Sloan Kettering Cancer Center 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Boulad F, Shore T, van Besien K, Minniti C, Barbu-Stevanovic M, Fedus SW, Perna F, Greenberg J, Guarneri D, Nandi V, Mauguen A, Yazdanbakhsh K, Sadelain M, Shi PA. Safety and efficacy of plerixafor dose escalation for the mobilization of CD34(+) hematopoietic progenitor cells in patients with sickle cell disease: interim results. Haematologica. 2018 May;103(5):770-777. doi: 10.3324/haematol.2017.187047. Epub 2018 Feb 1. Erratum in: Haematologica. 2018 Sep;103(9):1577.

Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT02193191 History of Changes
Other Study ID Numbers:	13-229
First Posted:	July 17, 2014
Last Update Posted:	April 11, 2018
Last Verified:	April 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:

Plerixafor; 13-229

Additional relevant MeSH terms:

Anemia, Sickle Cell; Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia	Hemoglobinopathies; JM 3100; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents