SCD Stem Cell Mobilization and Apheresis Using Motixafortide

Phase 1
Recruiting
Conditions
Interventions
Registration Number
NCT06442761
Lead Sponsor
St. Jude Children's Research Hospital
Brief Summary

This study is being done to see if the study drug, motixafortide, is safe in participants with sickle cell disease (SCD). Investigators also want to see if the drug will help the body increase the number of stem cells that can be collected for possible future transplant use.

PRIMARY OBJECTIVE
...

Detailed Description

This study is divided into 2 parts. Participants will be assigned to a part based on when they enroll. Early in the study, participants will be assigned to part A. Later in the study, participants will be assigned to part B. In both parts, participants will receive the study drug, motixafortide, by an injection under the skin. About 8 hours after the injecti...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
15
Inclusion Criteria
  • Participants with severe sickle cell disease (SCD) who are ≥18 years of age and willing to donate autologous hematopoietic stem cells (HSCs) for advancing future gene therapy for SCD after collection of back-up product. Severe SCD, for the purpose of this study, will be defined as participants who are receiving chronic transfusion therapy due to SCD related complications or are eligible for or currently enrolled on an allogeneic transplant protocol.

  • Participant must have a documented diagnosis of SCD with documentation of SCD genotype by medical history

  • Participants should either have a central line in place or be able to undergo apheresis without the necessity of the insertion of a central venous catheter

  • ECOG performance status/Karnofsky score/Lansky score >80

  • White blood cell (WBC) count >3.0 x 10^9/L, absolute neutrophil count (ANC) >1.0 x 10^9/L, and platelet count >150 x 10^9/L, and hemoglobin >7.0 gm/dL

  • Adequate renal function defined as serum/plasma creatinine < 1.5 mg/dL and an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m^2 based on the CKD-Epi equation or the St. Jude equation.

  • Adequate liver function defined as direct bilirubin < 2.5 times the upper limit of normal range; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times the upper limit of normal range.

  • Participant's cardiac function (i.e., ejection fraction >40%) and pulmonary status (i.e., no evidence of pulmonary hypertension) must be sufficient to undergo apheresis, as assessed by the Principal Investigator or an independent physician evaluating the participant.

  • Negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1/II

  • Feasible manual or automated exchange transfusion plan to achieve hemoglobin S (HbS) near 30% within one week of mobilization

  • Female participants of childbearing age should have a negative serum pregnancy test within one week of beginning motixafortide administration.

  • Participants of childbearing potential should agree to use of a highly effective form of contraception during treatment and for at least 1 month after the last dose of motixafortide. Women of childbearing potential must agree to use 2 methods of effective contraception: One barrier method (e.g. diaphragm, or condom or sponge, each of which are to be combined with a spermicide) and one hormonal method, unless she uses a highly effective method. Highly effective methods of contraception include:

    • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
    • Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
    • Intrauterine device (IUD)
    • Intrauterine hormone-releasing system (IUS)
    • Bilateral tubal occlusion
    • Vasectomised partner
    • Sexual abstinence.
Read More
Exclusion Criteria
  • Emergency room admission or hospitalization in the past 14 days prior to first dose of study drug
  • Major surgery in the past 30 days prior to first dose of study drug
  • Active and painful splenomegaly or splenomegaly (size greater than upper limit of normal on examination).
  • Participant who, by medical history, requires rare donor registry RBC units for transfusion, or is unable to receive routine transfusion. Eligible study participants must have undergone prior work-up for the presence of red cell alloantibodies and confirmation of available compatible blood product support
  • Known allergy to or contraindication for motixafortide administration, or medications routinely administered during apheresis
  • Participant who has had a prior autologous or allogeneic transplantation, inclusive of gene therapy
  • Active viral, bacterial, fungal, or parasitic infection.
  • History of cancer, excluding squamous carcinoma of the skin and cervical carcinoma in situ.
  • Participant who has received experimental therapy within 4 weeks prior to providing informed consent
  • Poorly controlled diabetes mellitus, as assessed by the Investigator
  • Concomitant treatment with alternative investigational agent unable to be held for 30 days
  • Unwillingness to use a highly effective method of contraception for 1 month after motixafortide
  • Pregnancy
  • Inability or unwillingness of research participant or legal guardian/ representative to give written informed consent.
  • Inability or unwillingness of research participant to hold hydroxyurea for 30 days prior to first dose of study drug
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Treatment-Arm A-Single DoseMotixafortidePart A: Participants who enroll early will be assigned to Part A. Part A participants will get one dose of the study drug and one stem cell collection process.
Treatment-Arm B-Two Daily DosesMotixafortidePart B: Participants who enroll later in the study will be assigned to Part B. Part B participants will get two doses of the study drug and two stem cell collection processes over two days (one on each day).
Primary Outcome Measures
NameTimeMethod
To assess the safety and tolerability of motixafortide in participants with sickle cell disease (SCD) as determined by the incidence of adverse events.0 - 30 days
Secondary Outcome Measures
NameTimeMethod
To recommend a phase 2 dosing strategy of one or two doses motixafortide in participants with SCD based on the incidence of adverse eventsthrough study completion, an average of 1 year
To determine the yield of CD34+ cells/kg after a single or daily dose of motixafortide in participants with SCD.1 - 2 days
To recommend a phase 2 dosing strategy for timing of apheresis based on peripheral blood CD34+ counts/uL after motixafortide administration in participants with SCDthrough study completion, an average of 1 year
To determine the mobilization effects as determined by peripheral blood CD34+ counts/uL after a single or daily dose of motixafortide in participants with SCD.1 - 2 days

Trial Locations

Locations (1)

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

© Copyright 2024. All Rights Reserved by MedPath