Tegavivint for Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Uncontrolled illness, CNS leukemia, others

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

Compensation: Varies

Number of Visits: 10

9 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial is to find out the best dose and side effects of tegavivint in treating patients with leukemia that has come back (relapsed) or does not response to treatment (refractory). Tegavivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tegavivint in combination with decitabine may help control the disease.

Will I have to stop taking my current medications?

The trial requires that you stop leukemia therapy for 14 days before starting tegavivint, but you may use hydroxyurea if needed until 24 hours before starting the trial and during the first cycle. The protocol does not specify about other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Tegavivint for Leukemia?

Decitabine, a component of the treatment, has shown effectiveness in improving survival and response rates in patients with acute myeloid leukemia (AML), especially in those who are not candidates for standard chemotherapy. Additionally, the combination of decitabine with cedazuridine has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), indicating its potential effectiveness in similar blood-related cancers. ^{1 2 3 4 5}

Is Tegavivint (also known as Decitabine, Dacogen, etc.) generally safe for humans?

Decitabine, used in older patients with acute myeloid leukemia, is generally well tolerated with common side effects like fever, low platelet count, and anemia. It has a relatively modest non-blood-related toxicity, making it a promising option for those who cannot undergo more intensive treatments. ^{1 2 3 5 6}

What makes the drug Tegavivint for Leukemia unique compared to other treatments?

Tegavivint, when combined with Decitabine, offers a novel approach by potentially enhancing the effects of Decitabine, a drug that reactivates silenced tumor suppressor genes in leukemia. This combination may provide a new option for patients who are not candidates for standard chemotherapy, offering a different mechanism of action compared to traditional treatments. ^{1 2 3 5 7}

Research Team

Tapan M Kadia

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with relapsed or refractory leukemia who haven't had leukemia treatment in the past 14 days (except hydroxyurea until starting this trial) can join. They must have acceptable liver and kidney function, a heart ejection fraction of at least 45%, and be physically able to participate (ECOG <=2). Women must not be pregnant, all participants must agree to use contraception, and they cannot have uncontrolled illnesses or hypersensitivity to the drugs used.

Inclusion Criteria

Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) - or =< 5 x ULN if related to leukemic involvement

I can take care of myself but might not be able to do heavy physical work.

I understand the study's requirements and have signed the consent form.

Exclusion Criteria

I do not have active, uncontrolled brain leukemia.

I am willing to use birth control during the study.

I do not have any severe illnesses or social situations that would prevent me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Dose Escalation)

Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

4 visits (in-person) per cycle

Treatment (Combination Cohort)

Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22 and decitabine IV over 30-60 minutes on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

5 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Decitabine
• Tegavivint

Trial Overview This phase I trial is testing Tegavivint combined with Decitabine for adults with leukemia that has returned after treatment or hasn't responded to previous treatments. The goal is to determine the best dose of Tegavivint and understand its side effects when used alongside Decitabine.

Participant Groups

Group I: Treatment (tegavivint, decitabine) Experimental Treatment 2 Interventions

PART I: Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. PART II: Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22 and decitabine IV over 30-60 minutes on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

Decitabine, administered at a dose of 20 mg/m² for 5 consecutive days, has been approved for older patients (≥65 years) with acute myeloid leukaemia (AML) who cannot undergo standard treatment, showing clinically meaningful improvements in overall survival after extended follow-up.

In a pivotal phase III trial, decitabine demonstrated significantly higher complete remission rates compared to standard treatment options like cytarabine, with a safety profile similar to cytarabine, including common side effects like fever and low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine: a review of its use in older patients with acute myeloid leukaemia. Curran, MP.[2021]

The optimal biologic dose (OBD) of decitabine for treating acute myeloid leukemia (AML) was determined to be 20 mg/m²/day, which showed limited nonhematologic toxicity and promising clinical activity, with a response rate of 44% among 25 patients.

Combining decitabine with valproic acid (VA) resulted in dose-limiting encephalopathy at lower doses of VA, indicating safety concerns, while the clinical responses were similar whether patients received decitabine alone or in combination with VA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. Blum, W., Klisovic, RB., Hackanson, B., et al.[2019]

In a phase 1 study involving 44 patients with myelodysplastic syndromes or chronic myelomonocytic leukaemia, the combination of oral decitabine and the CDA inhibitor cedazuridine successfully increased the bioavailability of decitabine, achieving pharmacokinetics similar to intravenous administration without increasing toxicity.

The study demonstrated that oral decitabine combined with cedazuridine produced effective dose-dependent demethylation and clinical responses comparable to intravenous decitabine, suggesting it could be a viable alternative treatment for myeloid disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Savona, MR., Odenike, O., Amrein, PC., et al.[2019]

Decitabine is an effective hypomethylating agent for treating acute myeloid leukemia (AML), significantly improving overall survival and response rates compared to standard care, based on results from the phase 3 DACO-016 trial with adult patients who are not eligible for standard chemotherapy.

The treatment is generally well tolerated and remains effective even in patients with adverse-risk karyotypes or TP53 mutations, making it a valuable option for those unfit for more intensive therapies, with potential for future combination treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia. Santini, V., Lübbert, M., Wierzbowska, A., et al.[2022]

Decitabine is a DNA methyltransferase inhibitor with a long history of antileukemic efficacy, particularly effective in treating acute myeloid leukemia in older patients or those unable to undergo intensive therapy.

The current dosing regimen of decitabine (20 mg/m² for 5 days) has been refined to minimize nonhematologic toxicity, making it a promising option for patients who may not tolerate more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine for acute myeloid leukemia. Marks, PW.[2018]

References

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

Decitabine/Cedazuridine: First Approval. [2021]

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

Decitabine: a review of its use in older patients with acute myeloid leukaemia. [2021]

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

Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. [2019]

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

An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. [2019]

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

The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia. [2022]

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

Decitabine for acute myeloid leukemia. [2018]

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

Long-term follow-up of a phase I study of high-dose decitabine, busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias. [2018]