Stem Cell Collection for Familial Platelet Disorder

Overseen By Chitra Hosing, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Cognitive impairments, Uncontrolled bleeding, MDS, 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: Unknown

4 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to safely collect stem cells in individuals with RUNX1 Familial Platelet Disorder, a genetic condition affecting blood clotting. The treatment, called Autologous CD34+ Hematopoietic Stem Cells Mobilization, uses medication to aid the body in producing and collecting these crucial stem cells. This trial targets those with a confirmed RUNX1-FPD diagnosis who experience blood clotting issues in daily life. Participants will receive injections over several days to facilitate stem cell collection. The trial aims to determine if this method is safe and effective for future treatments. As a Phase 1 trial, the research focuses on understanding how the treatment functions in people, offering participants the chance to be among the first to receive it.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have been treated with an investigational drug within 30 days of screening, you may not be eligible to participate.

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

Research has shown that using a person's own stem cells, known as autologous CD34+ hematopoietic stem cells, is generally safe. To collect these cells, the drug G-CSF is often used. G-CSF helps bone marrow produce more stem cells and is usually safe, though some may experience mild side effects like bone pain or headaches.

If needed, another drug, plerixafor, may be used. It helps move stem cells into the bloodstream and is also considered safe, though some may experience nausea or diarrhea.

Overall, these treatments have been used safely in other contexts. As this is an early-phase trial, the primary goal is to closely monitor any side effects and ensure the treatment's safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for Familial Platelet Disorder, which often focus on managing symptoms through blood transfusions and medications, the use of autologous CD34+ hematopoietic stem cells represents a more innovative approach. This treatment involves mobilizing and collecting the patient's own stem cells, which are then encouraged to multiply and repair the faulty blood cell production. Researchers are excited about this approach because it targets the root cause of the disorder rather than just alleviating symptoms, and it utilizes the body's own cells, potentially reducing the risk of immune rejection. Additionally, the inclusion of plerixafor as a mobilizing agent is noteworthy, as it enhances stem cell release into the bloodstream, potentially leading to more effective collection and treatment outcomes.

What evidence suggests that Autologous CD34+ Hematopoietic Stem Cells Mobilization might be an effective treatment for RUNX1-FPD?

Research has shown that using a person's own stem cells, known as CD34+ stem cells, can improve conditions like familial platelet disorder. In this trial, participants will undergo Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis. Studies have found that a higher dose of these stem cells is linked to better survival rates and a lower chance of disease recurrence. In cases like multiple myeloma, more stem cells helped patients recover important blood cells faster. The treatment often includes a growth factor, such as G-CSF, to collect more stem cells from the blood. These early findings suggest this method could enhance blood cell function in familial platelet disorder. ^{3 4 6 7 8}

Who Is on the Research Team?

Chitra Hosing

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with RUNX1 Familial Platelet Disorder, which affects blood clotting. Participants must be eligible to undergo procedures to collect stem cells from their own blood.

Inclusion Criteria

Participants with systolic blood pressure ≤ 170 mm Hg and diastolic blood pressure ≤ 95 mmHg

I am willing to follow the study's birth control rules.

Participants willing and able to provide informed consent, as appropriate

Exclusion Criteria

I have been diagnosed with MDS or a blood cancer.

I haven't taken any experimental drugs recently.

Participants unable to comply with the study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mobilization and Apheresis

Participants receive G-CSF injections on Days 1-5, with optional plerixafor on Day 5 or 6 for stem cell mobilization and collection

1 week

Daily visits for injections

Follow-up

Participants are monitored for safety and effectiveness after stem cell collection

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Autologous CD34+ Hematopoietic Stem Cells Mobilization

Trial Overview The study tests the safety of using drugs Plerixafor and G-CSF (filgrastim or biosimilar) to mobilize stem cells in the bloodstream and then collecting these cells through a process called Apheresis.

How Is the Trial Designed?

Group I: Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis Experimental Treatment 3 Interventions

On Days 1-5, participants will receive a Granulocyte colony-stimulating factor (G-CSF), such as filgrastim, as an injection or by vein over about 5 minutes. If the study doctor thinks it is needed, participants will also receive plerixafor as an injection under the skin on Day 5 (and 6, if you have 2 days of apheresis).

Autologous CD34+ Hematopoietic Stem Cells Mobilization is already approved in United States, European Union for the following indications:

Approved in United States as Autologous CD34+ Hematopoietic Stem Cells Mobilization for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• RUNX1 Familial Platelet Disorder (research)

Approved in European Union as Autologous CD34+ Hematopoietic Stem Cells Mobilization for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• RUNX1 Familial Platelet Disorder (research)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

RUNX1 Foundation

Collaborator

Trials

1

Recruited

4+

Published Research Related to This Trial

A risk-based approach using circulating CD34(+) cell counts effectively identified 35% of patients as high risk for poor hematopoietic stem cell (HSC) mobilization, allowing targeted use of plerixafor to improve outcomes.

Out of 159 patients, 95% successfully provided adequate HSC collections on the first attempt, and the use of plerixafor significantly reduced the need for remobilization, thus controlling costs and minimizing unnecessary treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A risk-based approach to optimize autologous hematopoietic stem cell (HSC) collection with the use of plerixafor. Abhyankar, S., DeJarnette, S., Aljitawi, O., et al.[2022]

Mobilizing hematopoietic stem and progenitor cells in the bloodstream can lead to faster and more efficient collection for transplantation, resulting in quicker recovery for patients compared to nonmobilized cells.

Current mobilization methods, such as G-CSF or GM-CSF, may not work for all donors, and research is ongoing to identify factors that inhibit mobilization, which could improve the effectiveness of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mobilization of blood stem cells. Kessinger, A., Sharp, JG.[2015]

A systematic review of 28 randomized controlled trials found that combining cyclophosphamide with growth factors like molgramostim or filgrastim significantly improves the yield of hematopoietic stem cells (HSCs), essential for successful autologous transplantation.

While some mobilization strategies increase CD34+ cell yield, they may also lead to higher toxicity, indicating that treatment plans should be tailored to individual patient needs and safety considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies. Sheppard, D., Bredeson, C., Allan, D., et al.[2022]

A randomized trial showed that combining granulocyte colony-stimulating factor (G-CSF) with stem cell factor (SCF) significantly improved the mobilization of CD34+ cells in heavily pretreated patients with lymphoma, compared to using G-CSF alone.

This combination therapy not only increased the total CD34+ cell dose collected but also enabled more patients to reach the optimal CD34+ cell dose needed for successful stem cell transplantation, highlighting the importance of tailored mobilization strategies for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management strategies for the hard-to-mobilize patient. Stiff, PJ.[2005]

A patient with β-thalassemia intermedia successfully underwent stem cell mobilization using plerixafor after initial attempts with G-CSF failed, demonstrating the potential of plerixafor in challenging cases.

Adjustments in apheresis techniques, including changes in centrifugation speed and collection depth, enabled the successful collection of sufficient stem cells despite the presence of abnormal red blood cells, leading to successful autologous transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harvesting autologous stem cells from a patient with red blood cell abnormalities of β-thalassemia intermedia. Sanford, K., Roseff, SD., Anderson, J., et al.[2014]

In a study of 74 patients with hematologic malignancies, 72% successfully collected enough stem cells during the first mobilization attempt, allowing for prompt engraftment within 10-12 days.

For patients who initially failed to collect adequate stem cells, administering high-dose G-CSF immediately led to an 88% success rate in achieving the target stem cell count, significantly increasing the collection rate from 0.16 to 0.61 CD34+ cells/kg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful PBSC mobilization with high-dose G-CSF for patients failing a first round of mobilization. Gazitt, Y., Freytes, CO., Callander, N., et al.[2004]

Granulocyte colony-stimulating factor (G-CSF) is the standard treatment for mobilizing stem cells before autologous transplantation, with a daily dose of 10 microg/kg starting 4 days prior to apheresis being the most common method.

Plerixafor, when used alongside G-CSF, has been shown to be more effective in achieving stem cell collection goals compared to G-CSF alone, particularly in patients at high risk for mobilization failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral blood stem cell mobilization tactics. Rosenbeck, LL., Srivastava, S., Kiel, PJ.[2010]

A study involving normal volunteers showed that combining rhIL-3 with rhG-CSF for progenitor cell mobilization is safe and well-tolerated, with adverse effects similar to those of the individual treatments.

The sequential administration of rhIL-3 followed by rhG-CSF significantly increased the number of circulating CD34+ cells, which are important for stem cell collection, making it an effective protocol for enhancing stem cell mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human interleukin-3 (rhIL-3) enhances the mobilization of peripheral blood progenitor cells by recombinant human granulocyte colony-stimulating factor (rhG-CSF) in normal volunteers. Huhn, RD., Yurkow, EJ., Tushinski, R., et al.[2017]

High-dose chemotherapy combined with stem cell support has significantly improved the procedures for harvesting hematopoietic stem and progenitor cells, leading to better outcomes in autologous transplantation.

The development of hematopoietic growth factors and new mobilizing drugs, like plerixafor, has optimized stem cell collection, reduced hospitalization times, and made the process more cost-effective for patients, especially those with poor mobilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hematopoietic stem cells mobilization: state of the art in 2011 and perspectives]. Bijou, F., Ivanovic, Z., Boiron, JM., et al.[2021]

Recent advancements in hematopoietic stem cell mobilization techniques have significantly improved practices in autologous transplantation, as reviewed by the SFGM-TC workshop in 2018.

The use of plerixafor has been specified in mobilization protocols, helping to achieve collection goals while minimizing the number of apheresis procedures, leading to a dramatic reduction in collection failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modalities of mobilization and hematopoietic stem cells objectives in autologous transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Brignier, A., Ader, V., Bellegarde, K., et al.[2021]

Peripheral blood stem cells (PBSC) are increasingly used for hematopoietic stem cell transplants, with mobilization strategies like chemotherapy and growth factors significantly increasing the yield of CD34+ cells, which are crucial for transplantation.

While PBSC collection is generally effective, it can lead to side effects such as citrate reactions, thrombocytopenia, and in rare cases, serious complications like spleen rupture, particularly in allogeneic donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mobilization and harvesting of peripheral blood stem cells. Moog, R.[2019]

In a study involving 40 patients with hematological malignancies, the biosimilar G-CSF (Zarzio(®)) was found to be as effective as the original G-CSF (Neupogen(®)) for mobilizing and collecting autologous peripheral blood stem cells after chemotherapy.

Both treatments resulted in similar outcomes regarding the number of CD34+ cells mobilized and collected, as well as the number of injections and procedures needed, suggesting that Zarzio(®) could be a more cost-effective option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience of autologous peripheral blood stem cell mobilization with biosimilar granulocyte colony-stimulating factor. Lefrère, F., Brignier, AC., Elie, C., et al.[2015]

Autologous hematopoietic stem cell transplantation is the standard treatment for various cancers, relying on effective collection of hematopoietic progenitor/stem cells (HPC) from peripheral blood after chemotherapy and growth factor mobilization.

Some patients struggle to mobilize enough HPCs for transplantation, necessitating alternative collection methods or marrow harvests, highlighting the importance of effective mobilization strategies not only in oncology but also in potential applications like cardiac regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell mobilization: a clinical protocol. Pesek, G., Cottler-Fox, M.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10247464/

Effect of Autograft CD34+ Dose on Outcome in Pediatric ... For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05409547?term=AREA%5BConditionSearch%5D(Gcsf)%20AND%20AREA%5BLastUpdatePostDate%5D%20RANGE%5B2020-08-26,MAX%5D&rank=6

A Clinical Study of Autologous Peripheral Blood Stem Cell ... Key issues to be addressed: To compare the efficiency of stem cell mobilization and hematopoietic system reconstruction between PEG-rhG-CSF and rrhG-CSF.

3. withpower.com withpower.com/trial/early-phase-1-blood-platelet-disorders-9-2024-53992

Stem Cell Collection for Familial Platelet Disorder What data supports the effectiveness of the treatment Autologous CD34+ Hematopoietic Stem Cells Mobilization for Familial Platelet Disorder? Research shows ...

4. nature.com nature.com/articles/s41408-024-01165-w

Optimal infused CD34+ cell dose in multiple myeloma ... Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1083879113004618

Optimizing Autologous Stem Cell Mobilization Strategies to ... A panel of experts convened to discuss the currently available data on autologous hematopoietic stem cell mobilization and transplantation and to devise ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06414889

Protocol Title: Safety and Feasibility of Autologous CD34+ ... Study Overview. Brief Summary. To evaluate the safety and feasibility of collecting hematopoietic stem cells (HSC) in participants with RUNX1-FPD ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11527997/

Optimal infused CD34+ cell dose in multiple myeloma ... High levels of circulating CD34+ cells at autologous stem cell collection are associated with favourable prognosis in multiple myeloma. Br J ...

8. nature.com nature.com/articles/s41409-025-02695-y

Autologous haematopoietic stem cell transplantation for ... This EBMT consensus aims to promote patient safety and harmonize procedures for AD patient selection, care, follow-up, clinical and immune ...