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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tegavivint for individuals with acute myeloid leukemia that has returned or isn't responding to current treatments. Researchers aim to determine the best dose and possible side effects when tegavivint is used alone and in combination with decitabine, a chemotherapy medication. Individuals who have tried other leukemia treatments without success might be suitable candidates for this trial. The trial seeks to determine if these drugs together can better control the disease. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tegavivint is generally well-tolerated. In one study, most side effects were mild, such as slight nausea or tiredness, and were not serious. Severe side effects appeared rarely, affecting only a few patients. Another study with liver cancer patients found that tegavivint mostly caused mild side effects, with no very severe reactions.

Decitabine also has a known safety record. Studies have found that the most common side effect is a drop in blood cell counts, which can lead to infections or fatigue. While serious side effects like infections or bleeding can occur, they are uncommon.

In summary, studies have shown that both tegavivint and decitabine are generally safe, with mild to moderate side effects being the most common. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard leukemia treatments that often focus on chemotherapy or targeted therapies, Tegavivint introduces a unique approach by targeting the beta-catenin pathway. This pathway is crucial in cancer cell growth and survival, and Tegavivint's ability to disrupt it offers a novel mechanism of action. Additionally, when combined with Decitabine, a standard hypomethylating agent, the duo has the potential to enhance treatment effectiveness by combining disruption of cancer cell growth with DNA demethylation. Researchers are excited about these treatments because they offer a fresh angle on tackling leukemia, potentially leading to better outcomes for patients who do not respond to current therapies.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that tegavivint holds promise for treating leukemia by blocking the Wnt/β-catenin pathway, which aids cancer cell growth. Studies have found that tegavivint can slow tumor growth and cause cancer cells to stop growing or die. Decitabine has proven effective for treating acute myeloid leukemia (AML), with some studies reporting a response rate of about 36.1% in newly diagnosed patients. In this trial, participants will receive either tegavivint alone or combined with decitabine. Together, these treatments may offer new hope for patients with recurrent or hard-to-treat leukemia. ^{4 6 7 8 9}

Who Is on the Research Team?

Tapan M Kadia

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12268998/

Oral decitabine/cedazuridine plus venetoclax for older or ... Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol 2015; 94: 1127–38. [DOI] ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212621000254

Efficacy of 10-day decitabine in acute myeloid leukemia Highlights · Real world outcomes using the 10 day decitabine regimen in AML are lacking. · 10-day decitabine had an ORR of 36.1% in AML in the upfront setting.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04657081

Study Details | NCT04657081 | Pharmacokinetics, Safety, ... The primary purpose of the study is to rule out drug-drug interactions between ASTX727 and venetoclax combination therapy by evaluating area under the curve ( ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6504

An all-oral regimen of decitabine-cedazuridine (DEC-C) ... The 30- and 60-day mortality rates were 3.0% and 9.9%, respectively. PK data confirmed no drug-drug interactions between oral DEC-C and VEN.

5. ashpublications.org ashpublications.org/bloodneoplasia/article/2/2/100071/535264/A-phase-2-study-of-decitabine-with-or-without

A phase 2 study of decitabine with or without carboplatin and ... Among 91 patients (44 relapsed/refractory), no significant grade 3 or 4 toxicities were observed. Response rates were 26.7% for DAC alone, 14.3% ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38452788/

Oral decitabine and cedazuridine plus venetoclax for older or ... Three deaths occurred in patients in remission (one sepsis, one gastrointestinal haemorrhage, and one respiratory failure) and were potentially treatment ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6551

Phase II trial of 10-day ASTX727 (decitabine/cedazuridine ... Conclusions: The 10-day ASTX727-VEN combination showed safety profile comparable to other HMA-VEN regimens in salvage setting. TP53 wild type, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2895778/

An update on the safety and efficacy of decitabine ... Data collected from this study demonstrated a median survival of 19.4 months by the closure of the study. The most common reported side effect was cytopenias.

9. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/833/499481/A-Phase-2-Study-of-the-Fully-Oral-Combination-of

A Phase 2 Study of the Fully Oral Combination of ASTX727 ... A Phase 2 Study of the Fully Oral Combination of ASTX727 (Decitabine/Cedazuridine) Plus Venetoclax for Older and/or Unfit Patients with Acute Myeloid Leukemia