Plerixafor for Sickle Cell Disease

No longer recruiting at 1 trial location

Overseen By Roni Tamari, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Active infection, Major surgery, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Plerixafor to determine if it can safely and effectively boost blood cell counts in people with sickle cell disease. While Plerixafor is already used in cancer patients to increase stem cells, it is not yet approved for sickle cell disease. The trial involves administering a single dose of Plerixafor and monitoring its effects on blood cells. Individuals with sickle cell disease confirmed by specific blood tests (SS or Sβ thalassemia) who feel generally well enough to participate might be suitable candidates. As a Phase 1 trial, this research aims to understand how Plerixafor works in people with sickle cell disease, offering a chance to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking an investigational drug, you must stop at least 4 weeks before joining the study.

Is there any evidence suggesting that Plerixafor is likely to be safe for humans?

Research has shown that plerixafor is generally safe for people with sickle cell disease. In various studies, patients tolerated plerixafor well, and researchers reported no major safety issues. One study found that plerixafor could safely aid in collecting stem cells from patients, potentially leading to new treatments for sickle cell disease.

The FDA has already approved plerixafor to increase blood stem cells in cancer patients, indicating its safety for humans.

Overall, early research suggests plerixafor is safe for use in sickle cell disease, but further studies are needed to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Researchers are excited about Plerixafor for sickle cell disease because it offers a unique approach to treatment. Unlike current therapies that often focus on managing symptoms or boosting fetal hemoglobin levels, Plerixafor works by mobilizing hematopoietic progenitor cells (HPCs) from the bone marrow into the bloodstream. This is significant because these HPCs can potentially be modified with a lentiviral vector to carry the normal ß-globin gene, which could address the genetic root of sickle cell disease. The possibility of directly correcting the genetic defect responsible for sickle cell disease is what makes this treatment particularly promising.

What evidence suggests that Plerixafor might be an effective treatment for sickle cell disease?

Research has shown that Plerixafor, the treatment under study in this trial, can increase stem cell numbers in people with sickle cell disease (SCD). In one study, 87% of participants with SCD successfully reached the target for stem cell increase, which is crucial for potential treatments. Another study found that 53% of SCD patients treated with Plerixafor achieved the desired stem cell levels in their blood. These stem cells integrate well into the body and function properly. These findings suggest that Plerixafor could improve stem cell availability in people with SCD. ^{2 3 6 7 8}

Who Is on the Research Team?

Roni Tamari, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with confirmed Sickle Cell Disease (SS or Sβ thalassemia). Participants must have a certain level of physical fitness, adequate organ and marrow function, and not be pregnant or breastfeeding. They should not have any major health issues that could affect study participation and must agree to use contraception.

Inclusion Criteria

My blood and kidney functions are within the required ranges.

I have confirmed Sickle Cell Disease, either SS or Sβ thalassemia.

I agree to use birth control during the study.

Exclusion Criteria

My heart's pumping ability is normal.

My kidney function is reduced with a creatinine clearance below 60 ml/min.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of subcutaneous plerixafor with peripheral blood studies conducted at specified intervals

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dose limiting toxicity

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Plerixafor

Trial Overview The trial is testing the safety and effectiveness of Plerixafor in patients with sickle cell disease. Plerixafor is already FDA-approved for cancer patients to increase blood stem cell counts before collection but hasn't been approved yet for those with sickle cell disease.

How Is the Trial Designed?

Group I: Plerixafor Experimental Treatment 1 Intervention

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.

Plerixafor is already approved in European Union, United States for the following indications:

Approved in European Union as Mozobil for:

• Autologous stem cell transplantation for patients with lymphoma and multiple myeloma

Approved in United States as Mozobil for:

• Use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

New York Blood Center

Collaborator

Trials

25

Recruited

28,400+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5927989/

Safety and efficacy of plerixafor dose escalation for the ... Eight of 15 patients (53%) with SCD treated with plerixafor reached the peripheral blood CD34 cell target count of at least 30 CD34+ cells/μL, including three ...

2. ashpublications.org ashpublications.org/bloodadvances/article/5/9/2403/475877/Disease-severity-impacts-plerixafor-mobilized-stem

Disease severity impacts plerixafor-mobilized stem cell ... Recent studies suggest that plerixafor mobilization and apheresis in patients with sickle cell disease (SCD) is safe and can allow ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8114546/

Disease severity impacts plerixafor-mobilized stem cell ... Plerixafor mobilization of HSCs is effective for most subjects with SCD. Eighty-seven percent of participants (n = 20) successfully met the ...

4. haematologica.org haematologica.org/article/view/9644

Safe and efficient peripheral blood stem cell collection in ... Our data suggest plerixafor mobilized HSC in SCD are enriched for long-term engrafting HSC, which is not true of HSC from SCD bone marrow (BM), ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02989701

Study Details | NCT02989701 | Pilot and Feasibility Trial of ... Plerixafor has been compared to G-CSF in a sickle cell mouse model, and results showed effective mobilization of HSC subsets, without neutrophil or endothelial ...

6. haematologica.org haematologica.org/article/view/8448

Plerixafor enables safe, rapid, efficient mobilization of ... Plerixafor can be safely used to mobilize hematopoietic stem cells in sickle cell patients; this finding opens up new avenues for treatment approaches.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7556661/

Safe and efficient peripheral blood stem cell collection in ... Our data suggest plerixafor mobilized HSC in SCD are enriched for long-term engrafting HSC, which is not true of HSC from SCD bone marrow (BM), supporting a ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03664830

Safety of Blood Stem Cell Mobilization With Plerixafor in ... Safety of Blood Stem Cell Mobilization With Plerixafor in Patients With Sickle Cell Disease (PISMO). ClinicalTrials.gov ID NCT03664830.