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

Primary Purpose

Sickle Cell Disease

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Plerixafor
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Plerixafor, 13-229

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Weill Cornell Medical College

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Plerixafor

Arm Description

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.

Outcomes

Primary Outcome Measures

safety
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.
efficacy
Efficacy is defined as 100% of evaluable patients reaching a PB CD34 concentration ≥ 30/uL.

Secondary Outcome Measures

Full Information

First Posted
July 15, 2014
Last Updated
August 8, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Sanofi, New York Blood Center, Weill Medical College of Cornell University, Duke University
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1. Study Identification

Unique Protocol Identification Number
NCT02193191
Brief Title
Escalation of Plerixafor for Mobilization of CD34+ Hematopoietic Progenitor Cells and Evaluation of Globin Gene Transfer in Patients With Sickle Cell Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2014 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Sanofi, New York Blood Center, Weill Medical College of Cornell University, Duke University

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Plerixafor, 13-229

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Plerixafor
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Plerixafor
Primary Outcome Measure Information:
Title
safety
Description
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.
Time Frame
up to 30 days
Title
efficacy
Description
Efficacy is defined as 100% of evaluable patients reaching a PB CD34 concentration ≥ 30/uL.
Time Frame
≥ 30/ul at either 6-12 hours or 24-48 hours post plerixafor.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roni Tamari, MD
Phone
646-608-3738
First Name & Middle Initial & Last Name or Official Title & Degree
Michel Sadelain, MD, PhD
Phone
212-639-6190
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roni Tamari, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roni Tamari, MD
Phone
646-608-3738
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Citations:
PubMed Identifier
34166998
Citation
Boulad F, Zhang J, Yazdanbakhsh K, Sadelain M, Shi PA. Evidence for continued dose escalation of plerixafor for hematopoietic progenitor cell collections in sickle cell disease. Blood Cells Mol Dis. 2021 Sep;90:102588. doi: 10.1016/j.bcmd.2021.102588. Epub 2021 Jun 15.
Results Reference
derived
PubMed Identifier
34160085
Citation
Avecilla ST, Boulad F, Yazdanbakhsh K, Sadelain M, Shi PA. Process and procedural adjustments to improve CD34+ collection efficiency of hematopoietic progenitor cell collections in sickle cell disease. Transfusion. 2021 Sep;61(9):2775-2781. doi: 10.1111/trf.16551. Epub 2021 Jun 23.
Results Reference
derived
PubMed Identifier
29419425
Citation
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.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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