STX-0712 for CMML and AML

Overseen By Head of Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Solu Therapeutics, Inc

Must be taking: Hydroxyurea

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Nicotine use, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 42

105 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a first-in-human, multicenter, open-label, phase 1 study to evaluate the safety, PK, PD and preliminary efficacy of STX-0712 in patients with advanced CMML and AML for whom there are no further treatment options known to confer clinical benefit.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received chemotherapy, biologic therapy, or wide-field radiation within 14 days of consent, and certain growth factors within 2 weeks prior to the first dose. Hydroxyurea may be continued up to 72 hours before the first dose and during the first cycle for some participants.

What data supports the effectiveness of the treatment STX-0712 for CMML and AML?

The research highlights the potential of immune-based therapies, like those using natural killer (NK) cells, in treating acute myeloid leukemia (AML). These therapies have shown promising results in early trials, suggesting that similar approaches could be effective for AML and possibly related conditions. ^{1 2 3 4 5}

Is STI-571 (imatinib mesylate) safe for use in humans?

STI-571, also known as imatinib mesylate, has been shown to be generally safe in humans, with minimal adverse effects reported in studies involving patients with chronic myelogenous leukemia (CML). It was well tolerated even in heavily pretreated patients, with a safety profile similar to previous trials. ^{6 7 8 9 10}

How is the drug STX-0712 different from other treatments for CMML and AML?

STX-0712 is unique because it may involve a novel mechanism or formulation not detailed in the available research, as there is no direct information on its specific action or components compared to existing treatments for CMML and AML. ^{9 11 12 13 14}

Research Team

Chief Medical Officer, MD, MSc, MBA

Principal Investigator

Solu Therapeutics

Eligibility Criteria

This trial is for patients with advanced blood cancers, specifically CMML and AML, who have no other treatment options known to be effective. The exact eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

Life expectancy of >2 months and stable enough to complete two cycles of STX-0712, in the opinion of the Investigator

Both females of child-bearing potential and males must agree to use acceptable contraceptive methods for the duration of time in the study and to continue to use acceptable contraceptive methods for 90 days after last STX-0712 infusion

Able to understand and willing to sign a written informed consent form

Exclusion Criteria

Received an investigational treatment within 30 days prior to dosing with STX-0712

Current active use of nicotine products including tobacco, nicotine patches or vaping products

Evidence of any other severe or uncontrolled systemic diseases, any other serious and/or unstable pre-existing medical conditions, psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive STX-0712 every 21 days to determine the maximum tolerated dose and/or minimum effective dose

12 months

Every 21 days

Dose Expansion

Participants receive STX-0712 every 21 days to evaluate safety, PK, PD, and preliminary efficacy

12 months

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• STX-0712

Trial Overview The study tests STX-0712's safety and effectiveness in treating certain blood cancers. It's a first-in-human trial meaning this drug hasn't been tested in people before. Patients will receive STX-0712 to see how their bodies react (PK/PD) and if it helps their condition.

Participant Groups

Group I: Dose Expansion in CMML Experimental Treatment 1 Intervention

STX-0712 will be administered every 21 days.

Group II: Dose Expansion in AML Experimental Treatment 1 Intervention

STX-0712 will be administered every 21 days.

Group III: Dose Escalation in CMML Patients Experimental Treatment 1 Intervention

STX-0712 will be administered every 21 days.

Group IV: Dose Escalation in AML Patients Experimental Treatment 1 Intervention

STX-0712 will be administered every 21 days.

Who Is Running the Clinical Trial?

Solu Therapeutics, Inc

Lead Sponsor

Findings from Research

Since 2017, the FDA has approved nine new agents for treating acute myeloid leukemia (AML), marking significant progress in AML therapy after decades of slow advancement.

Specific treatments for subsets of AML, such as all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia, have led to impressive 10-year survival rates of over 80%, demonstrating the efficacy of targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach. Kantarjian, HM., Kadia, TM., DiNardo, CD., et al.[2021]

In a study of 79 patients treated with CPX-351 for acute myeloid leukemia (AML), the treatment achieved a complete remission rate of 52% and a 60-day mortality rate of 18%, indicating its potential effectiveness in this patient population.

When compared to a matched cohort receiving standard intensive chemotherapy, CPX-351 showed similar rates of complete remission and overall survival, but a higher percentage of patients were able to undergo stem cell transplant, suggesting a possible advantage in treatment pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry. Bernal, T., Moreno, AF., de LaIglesia, A., et al.[2023]

In a phase I trial involving 20 patients with acute myeloid leukemia (AML), the combination of selinexor with high-dose cytarabine and mitoxantrone was found to be feasible and tolerable, with no dose-limiting toxicities observed at the target dose of 80 mg.

The treatment resulted in a 70% overall response rate, with 50% of patients achieving complete remission, indicating promising efficacy for selinexor in combination therapy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia. Wang, AY., Weiner, H., Green, M., et al.[2022]

In a study comparing leukaemic cells from six chronic myeloid leukaemia (CML) patients during chronic phase and blast crisis, the cells showed similar sensitivity to the drug STI571, indicating that intrinsic resistance is not a major factor in blast crisis.

Despite the similar sensitivity to STI571, patients in blast crisis generally experience only transient responses to the treatment, suggesting that other factors beyond drug sensitivity may contribute to treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity to the abl inhibitor STI571 in fresh leukaemic cells obtained from chronic myelogenous leukaemia patients in different stages of disease. Gambacorti-Passerini, C., Barni, R., Marchesi, E., et al.[2019]

Vaccination with autologous dendritic cells (DCs) derived from leukemic blasts in five AML patients was well tolerated, with no severe adverse effects reported, and resulted in stable conditions for three patients lasting 5.5 to 13 months.

The vaccination led to a significant increase in CD8+ T cells that specifically recognized a leukemia-associated antigen, indicating an enhanced immune response against AML, as evidenced by increased granzyme B release and a shift towards a type 1 T helper cell cytokine pattern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. Li, L., Giannopoulos, K., Reinhardt, P., et al.[2023]

References

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

Memory-like NK cells armed with a neoepitope-specific CAR exhibit potent activity against NPM1 mutated acute myeloid leukemia. [2022]

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

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia. [2022]

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

Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach. [2021]

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

A case of high-risk AML in a patient with advanced systemic mastocytosis. [2023]

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

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry. [2023]

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

Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT). [2015]

7. England pubmed.ncbi.nlm.nih.gov

A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Sensitivity to the abl inhibitor STI571 in fresh leukaemic cells obtained from chronic myelogenous leukaemia patients in different stages of disease. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Testing the safety of clinical-grade mature autologous myeloid DC in a phase I clinical immunotherapy trial of CML. [2023]

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

[Chronic myelogenous leukemia]. [2015]

11. China pubmed.ncbi.nlm.nih.gov

[Effects of ST1571 on the development of dendritic cells derived from bone marrow mononuclear cells in patients with chronic myeloid leukemia]. [2015]

12. Netherlands pubmed.ncbi.nlm.nih.gov

A monoclonal antibody to myelogenous leukemia: isolation and characterization. [2006]

13. Greece pubmed.ncbi.nlm.nih.gov

Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. [2023]

14. England pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade by a human MAb enhances the capacity of AML-derived DC to induce T-cell responses against AML cells in an autologous culture system. [2021]