Plerixafor for Sickle Cell Disease

(PISMO Trial)

Overseen By Joseph Rosenthal

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: G-CSF, Plerixafor

Disqualifiers: Alpha thalassemia, HIV, Malignancy, 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

5 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking G-CSF or plerixafor, you must stop at least 4 weeks before treatment.

What data supports the effectiveness of the drug Plerixafor (Mozobil) for treating sickle cell disease?

Plerixafor has shown effectiveness and safety in long-term use for WHIM syndrome, a condition involving immune system issues, which suggests it may have potential benefits for other conditions like sickle cell disease. ^{1 2 3 4 5}

Is plerixafor safe for use in humans?

Plerixafor, also known as Mozobil, has been used safely in humans for mobilizing stem cells in patients with conditions like lymphoma and multiple myeloma. Common side effects include mild reactions at the injection site and gastrointestinal issues, such as nausea. In studies involving patients with leukemia, adverse effects were generally mild and included nausea, dizziness, and fatigue. ^{6 7 8 9 10}

How is the drug Plerixafor unique in treating sickle cell disease?

Plerixafor is unique because it mobilizes stem cells without causing the dangerous side effects associated with other mobilization drugs, like granulocyte colony-stimulating factor, which can lead to life-threatening complications in sickle cell patients. ^{6 8 9 11 12}

What is the purpose of this trial?

The objective of this study is to investigate if up to two injections of plerixafor represent a safe and effective strategy to mobilize adequate numbers of CD34+ hematopoietic stem progenitor cells (HSPC) for autologous hematopoietic cell transplantation (HCT) in sickle cell disease (SCD) patients

Research Team

Leo Wang, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for individuals with sickle cell disease who weigh between 50-120 kg and have experienced severe pain crises or other complications like stroke, acute chest syndrome, or osteonecrosis. They should have good organ function and no history of certain conditions like alpha thalassemia, HIV/HTLV, uncontrolled infections, malignancy (except some skin cancers), recent major surgery, or prior gene therapy.

Inclusion Criteria

I have sickle cell disease with a specific genetic makeup.

Weight between 50 and 120 kg

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

Known hypersensitivity to plerixafor or any excipient contained in Mozobil

I have never received gene therapy.

Abnormal pulmonary function tests (adults with mild or moderate obstruction or restriction or diffusion defects are eligible, per Investigator discretion)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to two subcutaneous injections of plerixafor to mobilize hematopoietic stem cells

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• Plerixafor

Trial Overview The study tests whether two injections of Plerixafor are safe and effective in mobilizing enough CD34+ stem cells for autologous transplantation in patients with sickle cell disease. It aims to improve treatment by potentially enabling successful transplants.

Participant Groups

Group I: Plerixafor Experimental Treatment 1 Intervention

Up to two subcutaneous injections of plerixafor (starting dose level: 240 µg/kg/dose)

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Findings from Research

In a real-world study comparing new sickle cell disease treatments (L-glutamine, voxelotor, crizanlizumab) to hydroxyurea, the rates of adverse events (AEs) were found to be lower than those reported in clinical trials, indicating a potentially safer profile for these new agents.

The study revealed that the types of AEs varied by treatment, emphasizing the importance of effective communication between patients and physicians to better understand and manage patient-reported symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacovigilance assessment of adverse events associated with the use of hydroxyurea, L-glutamine, voxelotor, and crizanlizumab in sickle cell disease. Chen, M., Hankins, JS., Zhang, M., et al.[2023]

In a study of 1752 myelofibrosis (MF) patients, the incidence of blast phase (BP) was found to be 2.5% per year, with higher rates (4.3% and 4.5%) in patients with severe anemia (CTCAE grade 3/4 and grade 2, respectively).

Among 273 MF patients treated with ruxolitinib (RUX), the BP incidence was similar at 2.89% per year, indicating that the risk of BP in anemic MF patients is significant regardless of RUX treatment, which is important for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of blast phase in myelofibrosis according to anemia severity. Mora, B., Maffioli, M., Rumi, E., et al.[2023]

In a phase 2 trial involving 34 patients with myelofibrosis who did not respond to ruxolitinib, 32.4% achieved a significant reduction in spleen volume after 24 weeks of treatment with jaktinib, indicating its potential efficacy for ruxolitinib-refractory patients.

Jaktinib also improved hemoglobin levels in 50% of transfusion-independent patients with low baseline hemoglobin and reduced overall symptoms in 46.4% of patients, although it was associated with notable adverse events like thrombocytopenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are relapsed or refractory to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. Zhang, Y., Zhang, Q., Liu, Q., et al.[2023]

Plerixafor, approved by the FDA for use with G-CSF, significantly improves the mobilization of hematopoietic stem cells (HSC) for patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), with 59% of NHL patients and 72% of MM patients achieving the required cell collection in fewer apheresis sessions compared to placebo.

The treatment is generally safe, with common side effects including diarrhea, nausea, and fatigue, but the benefits in stem cell collection efficiency make it a valuable option for patients undergoing autologous transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Brave, M., Farrell, A., Ching Lin, S., et al.[2021]

Plerixafor, when used with G-CSF, significantly improves stem cell mobilization in patients with non-Hodgkin's lymphoma or multiple myeloma, allowing more patients to reach transplantation targets in fewer apheresis days, as shown in two randomized trials.

The treatment is generally well tolerated, with common side effects being mild injection-site reactions and gastrointestinal issues, making it a safe option for patients, especially those who are poor mobilizers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plerixafor: a review of its use in stem-cell mobilization in patients with lymphoma or multiple myeloma. Keating, GM.[2021]

Plerixafor, when combined with high-dose chemotherapy, was well tolerated in a phase 1 trial involving 19 children and young adults with relapsed or refractory acute leukemias and myelodysplastic syndrome, with no dose-limiting toxicities observed.

While plerixafor successfully mobilized leukemic blasts into the bloodstream in most patients, clinical responses were limited, with only three patients achieving remission, indicating that while the treatment is safe, its effectiveness in this heavily pretreated group was modest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study (POE 10-03). Cooper, TM., Sison, EAR., Baker, SD., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

A WHIM satisfactorily addressed. [2021]

2. Turkey pubmed.ncbi.nlm.nih.gov

Patterns of Hydroxyurea Prescription and Use in Routine Clinical Management of Polycythemia Vera: A Multicenter Chart Review Study [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Comparative pharmacovigilance assessment of adverse events associated with the use of hydroxyurea, L-glutamine, voxelotor, and crizanlizumab in sickle cell disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Incidence of blast phase in myelofibrosis according to anemia severity. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are relapsed or refractory to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients with Acute Myelogenous Leukemia Undergoing Allografting: Assessment of Safety and Tolerability. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

No evidence for cell activation or brain vaso-occlusion with plerixafor mobilization in sickle cell mice. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Plerixafor: a review of its use in stem-cell mobilization in patients with lymphoma or multiple myeloma. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study (POE 10-03). [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Plerixafor: AMD 3100, AMD3100, JM 3100, SDZ SID 791. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Patients' outcome after rescue plerixafor administration for autologous stem cell mobilization: a single-center retrospective analysis. [2021]