EXG34217 for Bone Marrow Failure Syndrome

Overseen By Minako Koga

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Elixirgen Therapeutics, Inc.

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: 6

Duration: Completed in prior study

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a long-term rollover follow-up study for Phase I/II study (Protocol EXG-US-01).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What safety data exists for EXG34217 (ruxolitinib) in humans?

Ruxolitinib, also known as EXG34217, has been studied for over a decade and is generally considered safe for treating conditions like myelofibrosis and polycythemia vera. Common side effects include anemia (low red blood cell count) and thrombocytopenia (low platelet count), but these rarely lead to stopping the treatment. Non-serious side effects like headaches and diarrhea have also been reported. ^{1 2 3 4 5}

How does the drug EXG34217 differ from other treatments for Bone Marrow Failure Syndrome?

EXG34217 may involve targeting specific genetic mutations like CSF3R, which are associated with certain blood disorders. This approach could offer a more personalized treatment option compared to traditional therapies, which often have significant side effects. ^{6 7 8 9 10}

Research Team

Kasiani Myers, MD

Principal Investigator

Cincinnati Children Hospital Medical Center

Eligibility Criteria

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 are willing to follow the new study's procedures.

Inclusion Criteria

Signed an Institutional Review Board (IRB) approved informed consent document indicating that they understand the purpose of, and procedures required by the study and are willing to participate in the study and comply with all study procedures and restrictions. Informed consent must be obtained from the subject prior to initiating procedures.

Have completed the 12-month visit of Study EXG-US-01.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants received EXG34217 treatment in the previous study EXG-US-01

Completed in prior study

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Every 6 months for 3 years, then annually for 2 years

Treatment Details

Interventions

• EXG34217

Trial Overview The intervention being studied is EXG34217. This trial serves as a long-term follow-up from an earlier Phase I/II study to monitor ongoing effects and gather more data on safety and efficacy.

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 phase 2 trial involving 51 patients with myelofibrosis who were intolerant to ruxolitinib, 43.2% of those treated with the novel JAK inhibitor jaktinib showed a significant reduction in spleen volume after 24 weeks.

Jaktinib also improved symptoms related to myelofibrosis, with 61.8% of patients experiencing a notable decrease in total symptom scores, although it was associated with some serious adverse events, including anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. Zhang, Y., Zhou, H., Duan, M., et al.[2023]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been the standard treatment for intermediate or high-risk myelofibrosis (MF) since its FDA approval in 2011, demonstrating significant efficacy in improving patient outcomes based on data from the phase 3 COMFORT trials.

The review highlights the importance of dose optimization and management of common side effects, such as anemia and thrombocytopenia, to maximize the safety and clinical benefits of ruxolitinib, supported by findings from subsequent trials like JUMP, ROBUST, EXPAND, and REALISE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. Verstovsek, S., Mesa, RA., Livingston, RA., et al.[2023]

In a phase 3b study involving 161 patients with polycythemia vera resistant or intolerant to hydroxyurea, ruxolitinib demonstrated a safety profile consistent with previous studies, with 37.9% of patients experiencing adverse events that required dose adjustments.

Ruxolitinib was effective, achieving hematocrit control in 45.3% of patients and significant spleen size reduction in 86.7%, indicating its potential as a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available. Foltz, L., Pica, GM., Zerazhi, H., et al.[2021]

In a study of 14 patients with myelofibrosis who received allogeneic hematopoietic cell transplantation after treatment with ruxolitinib, 71.4% experienced relief from myelofibrosis-related symptoms, and 64% had a significant reduction in spleen size.

Ruxolitinib treatment prior to transplantation was associated with a high engraftment rate of 93% and may improve outcomes by reducing inflammatory cytokines, potentially lowering the risk of graft failure and acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. Jaekel, N., Behre, G., Behning, A., et al.[2021]

Ruxolitinib, a JAK1/JAK2 inhibitor, was evaluated in a large phase 3b study (N = 2233) for treating myelofibrosis, including patients with low platelet counts, showing significant reductions in spleen size and symptoms.

The safety profile of ruxolitinib was consistent with previous studies, with common adverse events like anemia and thrombocytopenia, but these rarely led to treatment discontinuation, indicating it is a viable option for patients with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Al-Ali, HK., Griesshammer, M., Foltz, L., et al.[2021]

References

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

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. [2023]

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

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. [2021]

6. England pubmed.ncbi.nlm.nih.gov

CSF3R and CALR mutations in paediatric myeloid disorders and the association of CSF3R mutations with translocations, including t(8; 21). [2021]

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

Heterozygous germ line CSF3R variants as risk alleles for development of hematologic malignancies. [2022]

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

Hematopoietic growth factors for the treatment of aplastic anemia. [2019]

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

Identification of novel MECOM gene fusion and personalized therapeutic targets through integrative clinical sequencing in secondary acute myeloid leukemia in a patient with severe congenital neutropenia: a case report and literature review. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

Establishment of a new myeloid cell line with i(17q) as the sole chromosomal anomaly from the bone marrow of a patient with myelodysplastic syndrome. [2017]