EXG34217 for Bone Marrow Failure

Recruiting in Palo Alto (17 mi)

Overseen by Kasiani Myers, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Elixirgen Therapeutics, Inc.

Must not be taking: Danazol, Androgens

Disqualifiers: Cancer, Severe bone marrow failure, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests the safety and tolerability of EXG34217 in patients with bone marrow failure due to telomere biology disorders. The treatment involves collecting, processing, and reinfusing the patient's own blood cells to help improve their bone marrow function.

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.

What data supports the effectiveness of the drug EXG34217 for treating bone marrow failure?

Research on similar treatments, like recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF), shows that they can increase certain blood cells in patients with conditions like aplastic anemia, which is a type of bone marrow failure. This suggests that EXG34217 might also help improve blood cell counts in bone marrow failure. ^{1 2 3 4 5}

What safety data exists for EXG34217 (or similar treatments) in humans?

The treatment, similar to EXG34217, has generally been well tolerated, with bone pain being the most common side effect. Rarely, it has been associated with serious issues like splenic rupture and potential links to leukemia, but more long-term data is needed to confirm these risks. ^{5 6 7 8 9}

How is the drug EXG34217 different from other treatments for bone marrow failure?

EXG34217 is unique because it may involve the use of colony-stimulating factors (CSFs), which are proteins that help increase the production of blood cells by stimulating bone marrow. This approach is different from traditional treatments as it focuses on enhancing the body's natural ability to produce blood cells, potentially offering a novel way to address bone marrow failure. ^{5 10 11 12 13}

Research Team

Kasiani Myers, MD

Principal Investigator

Cincinnati Children Hospital Medical Center

Eligibility Criteria

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 have been diagnosed with a telomere biology disorder.

I am older than 18 years.

Exclusion Criteria

I cannot receive G-CSF and plerixafor treatments.

My bone marrow does not produce enough blood cells.

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

Trial Timeline

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

Treatment Details

Interventions

• EXG34217 (Unknown)

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.

Participant Groups

Group I: EXG34217 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Elixirgen Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

60+

Findings from Research

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]

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]

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 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]

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 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]

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]

References

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

Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage-colony-stimulating factor. [2021]

2. Korea (South) 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. [2015]

3. Japan 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. [2019]

4. China 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]. [2021]

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

Clinical applications of colony-stimulating factors. [2007]

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

Use and toxicity of the colony-stimulating factors. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

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

8. England 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. [2022]

9. Japan 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)]. [2007]

10. China pubmed.ncbi.nlm.nih.gov

[Serum level of granulocyte colony stimulating factor in severe aplastic anemia patients]. [2006]

11. Germany 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. [2012]

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

Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. A phase I-II trial. [2019]

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

Circulating colony-forming units of granulocytes/monocytes in patients with chronic myeloid leukemia before and during busulfan treatment. [2019]