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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called plerixafor for people with sickle cell disease. Researchers aim to determine if up to two injections of plerixafor can safely and effectively gather enough special stem cells for a future stem cell transplant. Suitable candidates have sickle cell disease and have experienced severe pain crises, chest syndrome, strokes, or regular blood transfusions in the past two years. As a Phase 1 trial, this research focuses on understanding how plerixafor works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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. Studies have found that plerixafor can safely aid in collecting important cells from the blood, which are used in transplants to help treat sickle cell disease. Most participants in these studies did not experience serious side effects.

However, a few individuals experienced vaso-occlusive crises, painful episodes common in sickle cell disease, at doses of 80 μg/kg and 240 μg/kg. Overall, the treatment appears well-tolerated, but awareness of these potential risks is important. ^{1 2 3 4 5}

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

Plerixafor is unique because it targets the movement of stem cells, which is different from typical treatments for sickle cell disease that focus on managing symptoms or boosting fetal hemoglobin levels. Unlike standard therapies like hydroxyurea or blood transfusions, plerixafor works by mobilizing stem cells from the bone marrow into the bloodstream. Researchers are excited about this treatment because it offers a new approach to potentially address the underlying cause of the disease, rather than just treating the symptoms.

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

Research has shown that plerixafor helps move important stem cells into the bloodstream in people with sickle cell disease (SCD). In one study, 53% of SCD patients treated with plerixafor reached the needed level of stem cells for a transplant. Another study found that patients collected an average of 4.0 million stem cells per kilogram of body weight, which is a suitable amount for a transplant. Plerixafor safely and effectively increases these stem cells in the blood, which is essential for a successful transplant. These findings suggest that plerixafor, which participants in this trial will receive, could be a promising option for preparing SCD patients for stem cell transplants. ^{1 2 3 4 6}

Who Is on the Research Team?

Leo Wang, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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 ... Plerixafor mobilization in this expanded cohort of participants with SCD from 2 clinical sites resulted in a median of 4.0 × 106 CD34+ cells/kg.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5927997/

Plerixafor enables safe, rapid, efficient mobilization of ... Plerixafor is highly efficient at mobilizing hematopoietic stem and progenitor cells from sickle cell disease patients. (A) Changes in white blood cell (WBC) ...

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. 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.