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.
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications, but you cannot participate if you have taken danazol or androgens within 60 days before the trial starts.
Is the drug EXG34217 a promising treatment for Bone Marrow Failure?Yes, EXG34217 is a promising treatment for Bone Marrow Failure because it is related to colony-stimulating factors, which have shown potential in increasing important blood cell counts and aiding recovery in patients with bone marrow issues.24589
What safety data is available for EXG34217 treatment?The safety data for treatments similar to EXG34217, such as granulocyte colony-stimulating factors (G-CSF) and granulocyte-macrophage colony-stimulating factors (GM-CSF), indicate that these drugs are generally well-tolerated. Common side effects include bone pain, and rare instances of splenic rupture, allergic reactions, and flares of autoimmune disorders. Long-term safety data is still needed to fully assess risks such as leukemia. Clinical trials have shown that these treatments can reduce the duration of neutropenia and associated complications without serious adverse reactions.146711
What data supports the idea that EXG34217 for Bone Marrow Failure is an effective treatment?The available research shows that treatments similar to EXG34217, like recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF), have been effective in increasing certain types of blood cells in patients with conditions like aplastic anemia. In one study, 10 out of 11 patients with aplastic anemia experienced significant increases in specific blood cells, which are important for fighting infections and overall health. However, the treatment did not significantly improve other blood components like red blood cells and platelets. This suggests that while EXG34217 may help increase some blood cell counts, further studies are needed to confirm its overall effectiveness and impact on health outcomes.34101213
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 am a woman who could become pregnant or am currently breastfeeding.
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.
I am currently receiving chemotherapy for my cancer.
My bone marrow test shows changes linked to MDS or AML.
I do not have any untreated serious infections.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: EXG34217Experimental Treatment1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Cincinnati Children's HospitalCincinnati, OH
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Who is running the clinical trial?
Elixirgen Therapeutics, Inc.Lead Sponsor
References
[Growth factors in therapy of life threatening leukopenia]. [2016]We have tested granulocyte/macrophage-colony-stimulating-factor (rhGM-CSF, fully glycosylated, Sandoz, Schering/Plough) in 40 patients with chemotherapy-induced neutropenia. The drug enhanced leukocyte recovery in 5 different dose levels (2-32 micrograms/kg body weight) if given by continuous intravenous infusion or subcutaneously for 5 days. Patients who received rhGM-CSF during neutropenic infections (n = 32) survived significantly better if they recovered leukocytes to at least 1.5 x 10(9)/l. In patients with myelodysplastic syndromes and excess of blasts (n = 82) remission could be induced in nearly 50% if the drug was given together with low dose cytosine arabinoside (LD-AraC). The results of these phase-II-studies show that rhGM-CSF is a safe drug which may save many patients from life-threatening situations during haematopoietic insufficiency.
Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. A phase I-II trial. [2019]To determine the hematopoietic effects and toxicity of recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with myelodysplastic syndromes.
Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage-colony-stimulating factor. [2021]Fifteen patients with refractory aplastic anemia or agranulocytosis received treatment with recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF) in doses from 4 to 64 micrograms/kg/d by continuous intravenous (IV) infusion. Ten of 11 evaluable patients with aplastic anemia had substantial increments in granulocytes, monocytes, and eosinophils associated with myeloid and eosinophilic hyperplasia in the bone marrow. Patients with pretreatment granulocytes greater than 0.3 x 10(9)/L had greater increments in circulating myeloid cells than patients with more severe granulocytopenia. Only one patient had improvement in erythrocytes and platelets. Blood counts fell to baseline after rhGM-CSF treatment was discontinued. Doses up to 16 micrograms/kg/d were relatively well tolerated in the absence of extreme leukocytosis. Fatigue and myalgia were common. Three patients developed pulmonary infiltrates that resolved with discontinuation of treatment. Patients tended to have recurrent inflammation in previously diseased tissues. These data indicate that rhGM-CSF will increase circulating granulocytes, monocytes, and eosinophils in patients with refractory aplastic anemia. Further studies are necessary to determine if rhGM-CSF treatment will reduce morbidity or improve survival.
Clinical applications of colony-stimulating factors. [2007]Colony-stimulating factors (CSFs) are a family of regulatory glycoprotein hormones that promote the proliferation and differentiation of hemopoietic progenitor cells and augment the functions of mature effector cells in vitro. The recent cloning of human genes and the availability of sufficient quantities of recombinant purified growth factors have made it possible to evaluate their therapeutic potential in cytopenic states. Initial studies with GM-CSF have demonstrated its ability to increase neutrophil, monocyte, and eosinophil counts in patients with acquired immune deficiency syndrome (AIDS), myelodysplastic syndrome (MDS), and aplastic anemia. Both GM-CSF and G-CSF reduce the duration of neutropenia following chemotherapy and accelerate hematopoietic recovery in patients undergoing intensive chemotherapy and autologous bone marrow transplantation. Studies are now ongoing to determine the optimal dose, route, schedule of administration, and long-term effects. While the appropriate settings for the use of different CSFs remain to be determined, the initial results of clinical trials are of great interest and suggest that hematopoietic growth factors will play an important role in several clinical arenas.
A phase I study of therapy with recombinant granulocyte-macrophage colony-stimulating factor administered by IV bolus or continuous infusion. [2012]Sixteen patients with primary or secondary bone marrow failure were treated with recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) given as either an intravenous bolus or by continuous infusion. The dose range studied was from 15 micrograms/m2/d to 960 micrograms/m2/d. Administration of rGM-CSF on a bolus schedule failed to elicit a hematologic response, but resulted in side effects of epigastric distress and eructation in over 30% of administered courses. Administration of rGM-CSF by continuous infusion resulted in a dose-dependent increase in the total leukocyte, granulocyte, and eosinophil counts. The mean maximal rise in granulocyte count was 8.5-fold. After cessation of therapy, blood counts returned to near baseline in most patients by 7 days. A 36 percent decrease from baseline in mean serum cholesterol level was observed in the continuous infusion group, but not in patients receiving rGM-CSF as an IV bolus. Fever, fatigue, and bone pain were dose-limiting in the continuous infusion group at a dose of 240 micrograms/m2/d. The maximally tolerated dose was 480 micrograms/m2/d. No life-threatening toxicities were observed in either group. Our data demonstrate that continuous infusion rGM-CSF is biologically active and non-toxic at a dose of 120 micrograms/m2/d in patients with bone marrow failure.
[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]A multicenter, randomized, double-blind controlled study was performed to evaluate the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rG.CSF) in reducing infectious morbidity and neutropenia induced by consolidation chemotherapy for acute myeloid leukemia (AML). One hundred and twenty-four eligible patients were randomized to receive either rG.CSF (5 micrograms/kg/d d.i.v.; 59 patients) or placebo (65 patients) for 14 days from the day after chemotherapy. All of them were included in the safety analysis, while 57 patients receiving rG.CSF and 64 patients receiving placebo were included in the efficacy analysis. The duration of neutropenia as well as the incidence of fever and febrile neutropenia, and frequency of antibiotic therapy required, were all significantly reduced in the rG.CSF group. No serious adverse reactions were encountered; there was no significant difference between the two groups in terms of incidence of adverse events. These results demonstrate that rG.CSF is beneficial to alleviate neutropenic episodes induced by consolidation chemotherapy in patients with AML.
Use and toxicity of the colony-stimulating factors. [2018]The colony-stimulating factors (CSFs) have emerged as effective drugs in a variety of clinical situations. These drugs stimulate the production and activity of haematopoietic cells in vitro and in vivo. Two members of this group, granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), have been approved in the US and Europe for use following cytotoxic chemotherapy and autologous bone marrow transplantation. Other uses of the CSFs include myelodysplastic syndromes, aplastic anaemia, the acquired immunodeficiency syndrome (AIDS) and cyclic and congenital neutropenias. Although CSFs have generally been well tolerated in clinical use there are a number of theoretical concerns, including disease acceleration, biased stem cell commitment and bone marrow exhaustion. New CSFs are currently under development. Combinations of growth factors in the future may maximise effectiveness while minimising toxicity.
Circulating colony-forming units of granulocytes/monocytes in patients with chronic myeloid leukemia before and during busulfan treatment. [2019]The number of colony-forming units of granulocytes/monocytes (CFU-GM) in the peripheral blood of 7 patients with chronic myeloid leukemia (CML) in chronic phase (CP) receiving standard doses of busulfan (BSF, 0.1-0.2 mg/kg/day p.o.) was compared to that found in 8 patients with CML in CP not previously treated in order to establish if non-myeloablative chemotherapy mobilizes committed granulomonocytic progenitor cells into the circulation. The number (mean +/- SEM) of spontaneous CFU-GM in untreated patients was similar to that recorded in 10 sex- and age-matched controls, 2.6 +/- 1.9 and 3.5 +/- 2.1, respectively. BSF-treated patients showed significantly more spontaneous CFU-GM (13.9 +/- 7.5) than controls and untreated patients. Addition of recombinant human granulocyte/monocyte colony-stimulating factor to cultures promoted colony growth in controls but not in untreated and BSF-treated patients. These data seemingly indicate that: 1) administration of standard non-myeloablative doses of BSF to patients with CML in CP mobilizes CFU-GM into the circulation and 2) BSF therapy selects a granulomonocytic colony-forming progenitor cell population with increased autonomous growth potential. These findings may contribute to the understanding of the therapeutic role of BSF in CML.
[Serum level of granulocyte colony stimulating factor in severe aplastic anemia patients]. [2006]To investigate the relationship between serum level of granulocyte colony stimulating factor (G-CSF) and clinical status, treatment outcome and prognosis in severe aplastic anemia (SAA-I) patients.
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]We compared the effects of the early-acting growth factors (GF), Flt-3 ligand (FL), c-Kit ligand (KL), and leukemia inhibitory factor (LIF), and the late-acting GF, granulocyte-colony stimulating factor (G-CSF) and megakaryocyte growth and development factor (MGDF), added alone in human long-term marrow culture (LTMC).
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]Granulocyte-colony stimulating factor (G-CSF) is widely administered to donors who provide peripheral blood stem cells (PBSC) for individuals who undergo hematopoietic stem cell transplants. Questions have been raised about the safety of G-CSF in this setting. Herein, the Research on Adverse Drug Events and Reports (RADAR) project investigators reviewed the literature on G-CSF-associated adverse events in healthy individuals or persons with chronic neutropenia or cancer. Toxicities identified included bone pain and rare instances of splenic rupture, allergic reactions, flares of underlying autoimmune disorders, lung injury and vascular events. Among healthy individuals, four patients developed splenic rupture shortly after G-CSF administration and three patients developed acute myeloid leukemia 1 to 5 years after G-CSF administration. Registry studies identified no increased risks of malignancy among healthy individuals who received G-CSF before PBSC harvesting. However, more than 2000 donors would have to be followed for 10 years to detect a 10-fold increase in leukemia risk. Our review identifies bone pain as the most common toxicity of G-CSF administration. There are questions about a causal relationship between G-CSF administration and acute leukemia, but more long-term safety data from database registries are needed to adequately evaluate such a relationship.
[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]To compare the efficacy and safety of two different regimens with recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with intensified immunosuppressive therapy (IIST) in severe aplastic anemia (SAA).
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]This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML).