Peripheral Blood Stem Cell Collection for Sickle Cell Disease (SCD) Patients

NCT03226691 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17012417-H-0124
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The constitution of blood relies upon hematopoietic stem cells (HSCs), which stay in the bone marrow and differentiate to all lineages of peripheral blood cells. HSC transplantation is the only curative option currently available for sickle cell disease (SCD) patients either via allogeneic HSC transplantation or HSC-targeted gene therapy. Granulocyte-colony stimulating factor (G-CSF)- mobilized HSCs are frequently utilized in the adult setting of HSC transplantation because of the faster hematologic recovery as compared to bone marrow. As an autologous HSC source for gene therapy, bone marrow harvest has been generally employed since G-CSF has been prohibitive in SCD patients due to granulocyte stimulation and the associated reports of vaso-occlusive crises, multi-organ failure, and death. However, when bone marrow harvest is used, the amounts of collected cells are limited and anesthesia is required. In order to obtain HSCs in large numbers without anesthesia, patients will undergo mobilization followed by large volume apheresis. Plerixafor is an alternative treatment for mobilization without direct stimulation to granulocytes, and it is theoretically applicable for SCD patients. The primary endpoint of this study is to obtain sufficient amounts of HSCs collected from the peripheral blood in SCD patients after plerixafor mobilization with an acceptable safety profile. The harvested products will be stored as backup for patients undergoing gene therapy as well as allogeneic HSC transplantation.

Conditions

Sickle Cell Disease

Keywords

Plerixafor; Leukapheresis; Mobilization; Stem Cells; Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sufficient Collection of Hemopoietic Stem Cells (HSCs) Without Serious Adverse Events

  Sufficient collection of HSCs (target 2.0x106 CD34+ cells/kg) from the PB after plerixafor mobilization without serious adverse events (SAEs)

  1 day

Study Arms (1)

Single Cohort - Plerixafor

EXPERIMENTAL

Plerixafor at a single dose of 240 microgram/kg

Drug: Plerixafor

Interventions

Plerixafor DRUG

Single-dose subcutaneous administration of plerixafor (Mozobil®) at 240 μg/kg

Also known as: Mozobil®

Single Cohort - Plerixafor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SCD patients who are 18 or older, and (a) planned to enroll in an active allogeneic HSCT study where back-up autologous HSCs are needed; OR (b) are eligible for an allogeneic HSCT study (i.e. have the same disease severity as group (a), but no active allogeneic HSCT study is available), and are willing to donate autologous HSCs for a future gene therapy, gene editing, or allogeneic HSCT study.
• Adequate renal function: serum/plasma creatinine \<1.5 mg/dL.
• Adequate liver function: direct bilirubin and ALT \<5 times the upper limit of normal range.
• Blood counts: WBC \>3,000/mm\^3, granulocytes \>1,000/mm\^3, hemoglobin\>7.0g/dL, platelets\>150,000/mm\^3.
• Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, have had a hysterectomy, post-menopausal, or absence of a menses for over a year.
• Meets NIH Department of Transfusion Medicine (DTM) eligibility criteria for blood component donation for in vitro research use (negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1).
• Ability to give informed consent to participate in the protocol.
• Female and male individuals of reproductive potential must agree to one of the contraceptive regimens stated above if sexually active

You may not qualify if:

• Pregnancy. Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, except those that have had a hysterectomy, post-menopausal, or an absence of a menses for over a year.
• Active viral, bacterial, fungal, or parasitic infection.
• History of cancer, excluding squamous carcinoma of the skin and cervical carcinoma in situ.
• Active and painful splenomegaly or splenomegaly (size greater than upper limit of normal) determined by ultrasound.
• Allergy to plerixafor.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• St. Jude Children's Research Hospital: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Leonard A, Sharma A, Uchida N, Stroncek D, Panch SR, West K, Molloy E, Hughes TE, Hauffe S, Taylor T, Fitzhugh C, Hankins JS, Wilson M, Tsai SQ, Weiss MJ, Hsieh M, Tisdale JF. Disease severity impacts plerixafor-mobilized stem cell collection in patients with sickle cell disease. Blood Adv. 2021 May 11;5(9):2403-2411. doi: 10.1182/bloodadvances.2021004232.

  PMID: 33956057 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: John Tisdale
• Organization: National Heart Lung and Blood Institute

johntis@nhlbi.nih.gov

+1 301 402 6497

Study Officials

• John F Tisdale, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2017
• First Posted: July 24, 2017
• Study Start: July 25, 2017
• Primary Completion: February 27, 2019
• Study Completion: February 27, 2019
• Last Updated: September 21, 2023
• Results First Posted: April 20, 2020

Record last verified: 2019-06-06

Locations

US (1)