CompletedPhase 1

Motixafortide and Natalizumab to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)

United States10 participantsStarted 2023-07-07

Plain-language summary

Hematopoietic stem cell (HSC)-based gene therapies now offer curative potential for patients with sickle cell disease (SCD), with decreased toxicity compared to allogeneic hematopoietic cell transplantation. However, effective HSC-based gene therapy depends on collecting sufficient HSCs to generate the therapeutic product, and currently available mobilization regimens carry unacceptable risk for patients with SCD or do not reliably yield optimal numbers of HSCs for gene therapy. The investigators hypothesize that HSC mobilization with motixafortide (CXCR4i) alone and the combination of motixafortide plus natalizumab (VLA-4i) will be safe and tolerable in SCD patients. In addition, the investigators hypothesize that combined CXCR4 and VLA-4 blockade with motixafortide plus natalizumab will result in a rapid, robust, and synergistic increase in HSC mobilization to peripheral blood (PB) in patients with SCD, when compared to motixafortide alone.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Adult patients at least 18 years old * Diagnosis of sickle cell disease (hemoglobin SS or Sβ0 genotype) * Receiving automated RBC exchanges via apheresis-capable central venous access or willing to have apheresis-capable venous access placed. * Able to hold hydroxyurea, voxelotor, and/or crizanlizumab for at least 60 days prior to mobilization * Able to hold iron chelation for at least 7 days prior to mobilization * ECOG performance status ≤ 1 * Normal bone marrow and organ function at screening as defined below: * Leukocytes ≥ 2,000/uL * Absolute neutrophil count ≥ 1,500/uL * Platelets ≥ 75,000/uL * AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN at time of screening * Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault * Baseline oxygen saturation ≥ 92% on room air * Left ventricular ejection fraction (LVEF) ≥ 45% (Of note, transthoracic echocardiogram (TTE) will not be required for study. However, if the treating physician has clinical concerns for active cardiac disease for which a TTE is clinically warranted as standard of care, then an EF of ≥ 45% will be required). * The effects of motixafortide and natalizumab on the developing human fetus are unknown. For this reason, women of childbearing 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, and 3 months after completion of the study. Should a woman become pregnant o…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs)

Timeframe: Through 28 days following administration of either motixafortide and/or natalizumab (estimated to be 8 weeks and 4 days)

Trial details

NCT IDNCT05618301

SponsorWashington University School of Medicine

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-06-24

View on ClinicalTrials.gov More Sickle Cell Disease trials