EXG34217 for Bone Marrow Failure

Overseen By Martine Francis

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Elixirgen Therapeutics, Inc.

Must not be taking: Danazol, Androgens

Disqualifiers: Cancer, Severe bone marrow failure, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EXG34217, designed to help individuals with bone marrow failure related to telomere biology disorders. The main goal is to assess the treatment's safety and the body's tolerance. Suitable candidates for this trial include those with mild to moderate bone marrow failure and a diagnosis of telomere biology disorders. As a Phase 1 trial, this research aims to understand how the treatment works in humans, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking danazol and androgens at least 60 days before starting. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that EXG34217 is likely to be safe for humans?

Research has shown that EXG34217 is under investigation for its potential to aid individuals with bone marrow failure due to certain genetic disorders. Early results suggest that this treatment might work by lengthening telomeres. Telomeres, which act as protective caps on the ends of chromosomes, can benefit some genetic conditions when extended.

Regarding safety, early studies indicate that patients generally tolerate EXG34217 well, with no serious side effects directly linked to the treatment. However, as this is a new therapy, ongoing research remains crucial to fully understand its safety. Participants should consult their healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for bone marrow failure, which often involve bone marrow transplants or medications to stimulate blood cell production, EXG34217 introduces a unique approach by using autologous CD34+ cells treated with EXG-001. This method focuses on enhancing the patient's own stem cells, potentially offering a more personalized and targeted therapy. Researchers are excited because this could lead to improved recovery times and better outcomes by directly addressing the root cause of the condition rather than just managing symptoms.

What evidence suggests that EXG34217 might be an effective treatment for bone marrow failure?

Research has shown that EXG34217, the investigational treatment in this trial, could help treat bone marrow failure linked to telomere biology disorders. Early results from past studies suggested that this treatment can lengthen telomeres, the protective ends of chromosomes. Short telomeres are linked to conditions like dyskeratosis congenita, which can cause severe bone marrow failure. These early findings are promising because longer telomeres might improve bone marrow cell health. Although more research is needed, this treatment offers hope for patients with these challenging conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Kasiani Myers, MD

Principal Investigator

Cincinnati Children Hospital Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with mild or moderate bone marrow failure due to telomere biology disorders. It's not for those with severe bone marrow failure, certain genetic abnormalities, uncontrolled infections, previous transplants, or who can't undergo specific treatments. Pregnant or breastfeeding women and patients on recent trials or cancer treatment are also excluded.

Inclusion Criteria

My bone marrow is not working well, but it's not severe.

I am older than 18 years.

I have been diagnosed with a telomere biology disorder.

Exclusion Criteria

I cannot receive G-CSF and plerixafor treatments.

I have had a bone marrow or stem cell transplant from a donor.

I am a woman who could become pregnant or am currently breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Peripheral blood mononuclear cells (PBMNCs) collection

Mobilization and apheresis of PBMNCs

1 week

1 visit (in-person)

Ex vivo cell processing

Processing of collected cells ex vivo

1 week

Processed cell infusion and post-infusion safety monitoring

Infusion of processed cells and monitoring for safety

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at Week 2, 3, 4, 5, and Months 1, 2, 3, 4, 5, 6, 9, and 12

What Are the Treatments Tested in This Trial?

Interventions

• EXG34217

Trial Overview The study tests the safety and effects of a drug called EXG34217 in patients with bone marrow failure linked to short telomeres. As an early-stage (Phase I/II) trial at a single center, it's designed to see how well participants tolerate this medication.

How Is the Trial Designed?

Group I: EXG34217 Experimental Treatment 1 Intervention

single autologous CD34+ cells contacted ex vivo with EXG-001

EXG34217 is already approved in United States for the following indications:

Approved in United States as EXG34217 for:

• Telomere biology disorders with bone marrow failure
• Dyskeratosis congenita

Who Is Running the Clinical Trial?

Elixirgen Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

60+

Published Research Related to This Trial

DA-3030, a recombinant human granulocyte colony-stimulating factor, was found to be effective in promoting neutrophil recovery in 26 patients with acute myelogenous leukemia (AML) after chemotherapy, with a median recovery time of 21 days.

The treatment was safe, with minimal side effects reported, primarily musculoskeletal pain and headache, indicating that DA-3030 can be a viable option for managing neutropenia in AML patients post-chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony-Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia. Min, YJ., Suh, CW., Park, KU., et al.[2015]

Flt-3 ligand (FL) and megakaryocyte growth and development factor (MGDF) were found to significantly stimulate early stages of blood cell development (hematopoiesis) in human long-term marrow cultures, with FL showing the strongest activity.

Granulocyte-colony stimulating factor (G-CSF) was effective in promoting the proliferation of mature progenitor cells in the granulo-monocyte lineage, highlighting its role in later stages of hematopoiesis, but its effects were dependent on the presence of a supportive stromal layer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proliferation of human progenitor cells in a long-term culture system is more efficiently sustained by the addition of Flt-3 ligand or megakaryocyte growth and development factor than by Kit ligand. Cartron, G., Binet, C., Hérault, O., et al.[2019]

Colony-stimulating factors (CSFs), like GM-CSF and G-CSF, have shown promising results in increasing blood cell counts in patients with conditions such as AIDS, myelodysplastic syndrome, and aplastic anemia, indicating their potential therapeutic benefits in cytopenic states.

Both GM-CSF and G-CSF have been effective in reducing the duration of neutropenia after chemotherapy and speeding up recovery of blood cell production in patients undergoing intensive treatments, highlighting their importance in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of colony-stimulating factors. Vadhan-Raj, S.[2007]

In a phase I-II trial involving 12 patients with myelodysplastic syndromes, daily subcutaneous injections of recombinant human G-CSF significantly increased blood leukocyte and neutrophil counts, with some patients experiencing a rise from severely low levels to normal ranges.

The treatment was well tolerated with minimal toxicity, and it effectively improved neutropenia and reduced transfusion needs in some patients, without any cases of acute leukemia developing during or shortly after the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. A phase I-II trial. Negrin, RS., Haeuber, DH., Nagler, A., et al.[2019]

Initiating rhG-CSF therapy earlier (before IIST) led to a significantly higher early response rate (67.5% vs. 37.5%) and reduced infection-related deaths (6.3% vs. 16.7%) in patients with severe aplastic anemia, indicating improved short-term safety and efficacy.

However, prolonged use of rhG-CSF in refractory patients was associated with a higher risk of progression to myelodysplastic syndromes or acute myeloid leukemia (22.3% vs. 3.71%), suggesting that while early treatment is beneficial, extended therapy may pose long-term risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of severe aplastic anemia with intensified immunosuppressive therapy and two different regimens with recombinant human granulocyte colony-stimulating factor: a retrospective study based on long-term follow-up]. Li, YM., Li, XX., Ge, ML., et al.[2021]

In a study involving 40 patients with chemotherapy-induced neutropenia, rhGM-CSF significantly improved leukocyte recovery when administered over 5 days, enhancing patient survival during neutropenic infections.

In patients with myelodysplastic syndromes, nearly 50% achieved remission when rhGM-CSF was combined with low-dose cytosine arabinoside, indicating its potential effectiveness in treating hematopoietic insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Growth factors in therapy of life threatening leukopenia]. Gerhartz, H.[2016]

In a study of 15 patients with refractory aplastic anemia or agranulocytosis, treatment with recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF) significantly increased levels of granulocytes, monocytes, and eosinophils, particularly in patients with higher baseline granulocyte counts.

While rhGM-CSF was generally well tolerated at doses up to 16 micrograms/kg/d, common side effects included fatigue and myalgia, and some patients experienced pulmonary infiltrates that resolved after stopping treatment, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage-colony-stimulating factor. Champlin, RE., Nimer, SD., Ireland, P., et al.[2021]

In a study of 36 patients with severe aplastic anemia (SAA-I), 75% had elevated serum levels of granulocyte colony stimulating factor (G-CSF) before treatment, which correlated with better treatment outcomes.

Measuring serum G-CSF levels can be a useful tool for assessing the clinical status and prognosis of patients with severe aplastic anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Serum level of granulocyte colony stimulating factor in severe aplastic anemia patients]. Chen, G., Shao, Z., Zhang, Y.[2006]

In a study of 7 patients with chronic myeloid leukemia (CML) receiving busulfan treatment, the number of granulocyte/monocyte progenitor cells (CFU-GM) in their blood was significantly higher compared to untreated patients and controls, indicating that busulfan effectively mobilizes these cells into circulation.

The results suggest that busulfan not only increases the number of CFU-GM but also selects for a progenitor cell population with enhanced growth potential, which may have important implications for the treatment of CML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating colony-forming units of granulocytes/monocytes in patients with chronic myeloid leukemia before and during busulfan treatment. López-Karpovitch, X., Cárdenas, R., Piedras, J.[2019]

Colony-stimulating factors (CSFs), particularly G-CSF and GM-CSF, are effective in stimulating the production of blood cells and are approved for use after chemotherapy and bone marrow transplants, showing their efficacy in various clinical situations.

While CSFs are generally well tolerated, there are concerns about potential risks such as disease acceleration and bone marrow exhaustion, highlighting the need for careful monitoring and the development of new CSFs and combinations to enhance effectiveness and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and toxicity of the colony-stimulating factors. Schriber, JR., Negrin, RS.[2018]

G-CSF is commonly used to stimulate stem cell donation but can cause side effects, with bone pain being the most frequent, and rare but serious risks like splenic rupture and potential links to acute myeloid leukemia.

While registry studies show no increased cancer risk in healthy donors after G-CSF, long-term follow-up of over 2000 donors is necessary to fully assess any potential increase in leukemia risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project. Tigue, CC., McKoy, JM., Evens, AM., et al.[2022]

Continuous infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) in 16 patients with bone marrow failure led to a significant dose-dependent increase in white blood cell counts, with a maximum granulocyte count increase of 8.5-fold.

In contrast, rGM-CSF administered as an intravenous bolus did not produce a hematologic response and caused side effects in over 30% of cases, highlighting that continuous infusion is a more effective and safer method of administration for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of therapy with recombinant granulocyte-macrophage colony-stimulating factor administered by IV bolus or continuous infusion. Rifkin, RM., Hersh, EM., Salmon, SE.[2012]

In a study involving 124 patients with acute myeloid leukemia (AML), recombinant human granulocyte colony-stimulating factor (rG.CSF) significantly reduced the duration of neutropenia and the incidence of febrile neutropenia compared to a placebo.

The treatment with rG.CSF did not lead to any serious adverse reactions, indicating it is a safe option for alleviating neutropenic episodes induced by chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A randomized double-blind controlled study of recombinant human granulocyte colony-stimulating factor in patients with neutropenia induced by consolidation chemotherapy for acute myeloid leukemia. (rG.CSF clinical study group)]. Takeshita, A., Ohno, R., Hirashima, K., et al.[2007]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04211714

NCT04211714 | Study to Evaluate of EXG34217 in Patients ... This is a Phase I/II, open label, single center study to assess the safety and tolerability of EXG34217 in bone marrow failure patients with telomere biology ...

2. elixirgentx.com elixirgentx.com/elixirgen-therapeutics-publishes-early-results-showing-telomere-elongation-in-first-gene-therapy-trial-for-telomere-biology-disorders/

Elixirgen Therapeutics Publishes Early Results Showing ... TBDs, such as dyskeratosis congenita, can lead to serious conditions including bone marrow failure due to severely affecting the ability of ...

3. withpower.com withpower.com/trial/phase-1-bone-marrow-failure-disorders-6-2023-9821a

EXG34217 for Bone Marrow Failure Syndrome This trial is for individuals with Bone Marrow Failure Syndrome, Pancytopenia, or Telomere Biology Disorders who have completed a previous study (EXG-US-01) and ...

4. globenewswire.com globenewswire.com/news-release/2025/09/01/3142261/0/en/Bone-Marrow-Failure-Market-Growth-Accelerates-with-Advances-in-Cell-and-Gene-Therapy-DelveInsight.html

Bone Marrow Failure Market Growth Accelerates with ... The bone marrow failure market is witnessing steady growth driven by the increasing prevalence of aplastic anemia, myelodysplastic syndromes ...

5. synapse.patsnap.com synapse.patsnap.com/article/elixirgen-therapeutics-gets-rare-pediatric-disease-status-for-exg-34217-in-dyskeratosis-congenita-and-telomere-disorders

Elixirgen Therapeutics Gets Rare Pediatric Disease Status ... ... bone marrow failure and other serious health conditions,” Ko stated. ... of diseases and the potential effectiveness of EXG-34217. RPDD is ...

6. scienceblog.cincinnatichildrens.org scienceblog.cincinnatichildrens.org/first-gene-therapy-trial-for-telomere-biology-disorders-shows-promising-results/

First Gene Therapy Trial for Telomere Biology Disorders ... One example of a TBD is dyskeratosis congenita, which can lead to bone marrow failure by interfering with the ability of hematopoietic stem ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/elixirgens-gene-therapy-shows-promise-in-telomere-biology-disorders/

Elixirgen's gene therapy shows promise in telomere ... Elixirgen Therapeutics' treatment for a set of genetic conditions that can lead to bone marrow failure has been able to elongate the caps of chromosomes in two ...