18 Participants Needed

Nerofe for Acute Myeloid Leukemia and Myelodysplastic Syndrome

JW
AT
Overseen ByAmber Thomassen, APRN-BC
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This trial tests NEROFE, a new drug given through an IV, on patients with certain blood cancers to find a safe dose and see if it helps control their cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you can continue using hydroxyurea if needed. If you are on systemic steroids or other immunosuppressants, you may need to stop them before starting the trial.

What data supports the effectiveness of the drug Nerofe for treating Acute Myeloid Leukemia and Myelodysplastic Syndrome?

Research on similar treatments shows that targeting specific receptors on leukemia cells can effectively kill drug-resistant cancer cells. For example, a fusion protein targeting GMCSF receptors has been shown to kill chemotherapy-resistant leukemia cells, suggesting that Nerofe, which may work in a similar way, could be effective.12345

Is Nerofe safe for humans?

The research mentions that a similar treatment using a diphtheria toxin fusion protein showed severe dose-dependent toxicity to organs like the liver, kidney, and lung in animal studies, but lower doses were used to avoid these effects. This suggests that while there may be potential safety concerns at higher doses, lower doses might be safer.15678

How is the drug Nerofe different from other treatments for acute myeloid leukemia and myelodysplastic syndrome?

Nerofe, also known as Tumor-Cells Apoptosis Factor (TCApF), is unique because it targets apoptotic signaling pathways, which are involved in the process of programmed cell death. This approach may offer a novel way to treat acute myeloid leukemia and myelodysplastic syndrome by potentially overcoming chemotherapy resistance seen in some patients.910111213

Eligibility Criteria

Adults with advanced Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) who haven't responded to standard treatments can join. They must have a certain level of disease risk, be in fair health, and their organs need to function well. People with severe liver or kidney issues, very high white blood cell counts without control measures, or poor venous access for blood sampling cannot participate.

Inclusion Criteria

My MDS did not improve after 4 HMA cycles, or I can't tolerate HMA.
Suitable venous access to allow for all study related blood sampling (safety and research).
I am able to care for myself and perform daily activities.
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

NEROFE is administered three times per week on alternate days for up to 12 cycles, with dosage determined by body surface area.

12 cycles (each cycle is 4 weeks)
Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a minimum follow-up of 30 days after the last dose.

4 weeks
1 visit (in-person)

Long-term follow-up

Participants are followed for the resolution of any ongoing adverse events after the initial follow-up period.

Treatment Details

Interventions

  • Nerofe
Trial OverviewThe trial is testing NEROFE, a new hormone-peptide treatment for MDS and AML. It's given intravenously three times weekly based on body size. The study aims to find the safest dose that works best (RP2D).
Participant Groups
1Treatment groups
Experimental Treatment
Group I: NEROFEExperimental Treatment1 Intervention
Dose Level - Nerofe Dose -1 - 6mg/m2 1. - 12 mg/m2 2. - 24 mg/m2 3. - 48 mg/m2 4. - 96 mg/m2 5. - 150mg/m2

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

🇺🇸
Approved in United States as Nerofe for:
  • Acute Myelogenous Leukemia (AML)
  • Myelodysplastic Syndrome (MDS)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Immune System Key Ltd

Lead Sponsor

Trials
5
Recruited
70+

University of Miami Sylvester Comprehensive Cancer Center

Collaborator

Trials
11
Recruited
2,700+

Findings from Research

The recombinant diphtheria toxin-human granulocyte macrophage colony-stimulating factor chimeric fusion protein (DTctGMCSF) effectively targets and induces rapid cell death in chemotherapy-resistant acute myeloid leukemia (AML) cells, showing promise for patients with resistant forms of the disease.
DTctGMCSF may offer a new treatment option for AML patients whose leukemia has recurred and become resistant to standard chemotherapy, potentially improving outcomes for this challenging patient population.
Induction of apoptosis in multidrug-resistant and radiation-resistant acute myeloid leukemia cells by a recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor receptor.Perentesis, JP., Waddick, KG., Bendel, AE., et al.[2007]
In a multicenter trial involving 640 patients with newly diagnosed acute myeloid leukemia (AML), the addition of granulocyte colony-stimulating factor (G-CSF) to chemotherapy improved disease-free survival rates, showing 42% at four years compared to 33% without G-CSF.
While G-CSF did not significantly enhance overall survival for all patients, it notably benefited those with standard-risk AML, leading to a 45% survival rate at four years versus 35% for those not receiving G-CSF.
Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia.Löwenberg, B., van Putten, W., Theobald, M., et al.[2022]
The novel recombinant chimeric fusion toxin DTctGMCSF effectively targets and kills acute myeloid leukemia (AML) cells that are resistant to conventional therapies, including those with multi-drug resistance and p53 deficiencies, with an IC50 of 1-10 ng/ml.
DTctGMCSF demonstrated selective cytotoxicity against over 99% of primary leukemic progenitor cells from therapy-refractory AML patients while sparing normal hematopoietic progenitor cells, suggesting a promising therapeutic option for resistant myeloid leukemias.
Granulocyte-macrophage colony-stimulating factor receptor-targeted therapy of chemotherapy- and radiation-resistant human myeloid leukemias.Perentesis, JP., Bendel, AE., Shao, Y., et al.[2019]

References

Induction of apoptosis in multidrug-resistant and radiation-resistant acute myeloid leukemia cells by a recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor receptor. [2007]
Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. [2022]
Granulocyte-macrophage colony-stimulating factor receptor-targeted therapy of chemotherapy- and radiation-resistant human myeloid leukemias. [2019]
Smac mimetic induces cell death in a large proportion of primary acute myeloid leukemia samples, which correlates with defined molecular markers. [2021]
In vivo targeting of leukemic cells using diphtheria toxin fused to murine GM-CSF. [2019]
The role of myeloid growth factors in acute leukemia. [2019]
CCND1-BCL2 Gene Network: A direct target of Amifostine in human acute megakaryocytic leukemia cells. [2018]
Use of white blood cell growth factors and risk of acute myeloid leukemia or myelodysplastic syndrome among elderly patients with non-Hodgkin lymphoma. [2021]
Diagnosis and management of core-binding factor leukemias. [2007]
Prognostic markers in core-binding factor AML and improved survival with multiple consolidation cycles of intermediate-/high-dose cytarabine. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
KIT exon 17 mutations are predictive of inferior outcome in pediatric acute myeloid leukemia with RUNX1::RUNX1T1. [2023]
12.United Statespubmed.ncbi.nlm.nih.gov
Advances in molecular genetics and treatment of core-binding factor acute myeloid leukemia. [2022]
Deregulated apoptosis signaling in core-binding factor leukemia differentiates clinically relevant, molecular marker-independent subgroups. [2013]