DEC-C + Thioguanine for AML

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph Jurcic

Must not be taking: Thioguanine

Disqualifiers: CNS involvement, HIV, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two medications, oral decitabine-cedazuridine and thioguanine, is safe and effective for treating acute myeloid leukemia (AML) that has returned or not responded to previous treatments. Initially, the trial will test different doses to identify the highest safe amount, then use that dose to further evaluate the combination's effectiveness against AML. Suitable participants have AML that did not improve with past treatments or recurred after treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop any anti-leukemic therapy, including investigational therapies, at least 14 days before starting the study treatment. However, you can continue using hydroxyurea to control blood counts during the induction cycles.

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

Research has shown that decitabine-cedazuridine (Inqovi®) is approved for adults with certain blood disorders, indicating it is generally well-tolerated. For acute myeloid leukemia (AML), researchers are testing this drug with thioguanine to assess its safety and effectiveness.

In past studies, decitabine-cedazuridine did not cause severe side effects when used for other conditions. However, its combination with thioguanine remains under close observation. The trial includes a "safety lead-in" phase to determine the highest safe dose by testing different amounts to ensure participants do not experience serious side effects.

If the initial doses cause too many issues, researchers will reduce the dose to find a safer level. This careful approach protects participants and ensures the treatment remains as safe as possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for acute myeloid leukemia (AML) that primarily involve chemotherapy drugs like cytarabine and daunorubicin, this new treatment combination of Decitabine-Cedazuridine and Thioguanine offers a novel approach. Decitabine-Cedazuridine is a unique formulation that allows for oral administration, making treatment potentially more convenient and less invasive than traditional intravenous chemotherapy. Additionally, Decitabine-Cedazuridine works by modifying DNA to slow cancer cell growth, while Thioguanine targets the DNA replication process, potentially enhancing the overall anti-leukemia effect. Researchers are excited about this combination because it could improve patient outcomes with a more manageable treatment regimen.

What evidence suggests that this treatment might be an effective treatment for AML?

In this trial, researchers are exploring whether combining decitabine-cedazuridine (Inqovi®) and thioguanine (Tabloid®) can more effectively treat acute myeloid leukemia (AML). Research has shown that decitabine-cedazuridine may treat AML, particularly in patients whose cancer has returned or resisted previous treatments, by slowing or stopping cancer cell growth. Studies also indicate that thioguanine can combat leukemia by interfering with cancer cells' DNA, potentially halting their growth. Early results from this trial suggest this combination could be effective, but further research is needed to confirm its benefits and safety. ^{1 2 3 4 6}

Who Is on the Research Team?

Joseph Jurcic

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for patients with acute myeloid leukemia (AML) whose disease has returned or hasn't responded to previous treatments. The study aims to ensure participants can handle the highest safe dose of medications.

Inclusion Criteria

Able to provide informed consent

My organs are functioning well.

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5x the upper limit of normal (ULN)

Exclusion Criteria

Known hypersensitivity to DEC-C or thioguanine

Significant medical diseases or comorbidities, in the opinion of the investigator, that would preclude the safe participation in the study

I currently have an infection that isn't under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Participants receive different doses of thioguanine and decitabine-cedazuridine to identify the highest safe doses

8-12 weeks

Phase II Treatment

Participants receive the maximum tolerated dose of the drug combination to explore anti-leukemia activity and safety

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine-Cedazuridine
• Thioguanine

Trial Overview The study tests if oral decitabine-cedazuridine (Inqovi®) combined with thioguanine (Tabloid®) is effective and tolerable for AML patients. It's a phase II trial that starts by confirming the safety of the maximum dose before proceeding.

How Is the Trial Designed?

Group I: Safety Lead-In Experimental Treatment 2 Interventions

Groups of participants will receive different doses of thioguanine and decitabine-cedazuridine to identify the highest doses that can be given safely. The highest doses that are safe will then be used in the phase II portion of the clinical trial. If no dose is found to be safe, the study will be stopped. A phase II expansion cohort will be enrolled to further explore the combination's anti-leukemia activity and safety and will proceed at the maximum tolerated dose defined in the initial Safety Cohort.

Decitabine-Cedazuridine is already approved in United States, European Union for the following indications:

Approved in United States as Inqovi for:

• Myelodysplastic syndromes (MDS)
• Chronic myelomonocytic leukemia (CMML)

Approved in European Union as Inqovi for:

• Adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anaemia, refractory anaemia with ringed sideroblasts, refractory anaemia with excess of blasts, refractory anaemia with excess of blasts in transformation to acute myeloid leukaemia), and intermediate-1, intermediate-2 and high-risk International Prognostic Scoring System groups.

Who Is Running the Clinical Trial?

Joseph Jurcic

Lead Sponsor

Trials

3

Recruited

2+

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

In a study of 12 patients with relapsed or refractory acute myeloid leukemia (AML), a combination of decitabine and gemtuzumab ozogamicin resulted in a 42% complete response rate, with five patients achieving complete remission and undergoing stem cell transplantation.

The treatment was well tolerated, with only mild nonhematologic toxicity observed, suggesting that this regimen could be a promising option for further investigation in larger controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine combined with fractionated gemtuzumab ozogamicin therapy in patients with relapsed or refractory acute myeloid leukemia. Chowdhury, S., Seropian, S., Marks, PW.[2019]

Decitabine (DAC) and arsenic trioxide (As2O3) both effectively inhibit the proliferation of human acute myeloid leukemia (AML) MV4-11 cells in a dose-dependent manner, with IC50 values of 2.409 µmol/L for DAC and 2.364 µmol/L for As2O3.

The combination of DAC and As2O3 significantly enhances the inhibition of cell proliferation and induces a much higher apoptotic rate (51.13%) compared to either drug alone, indicating a synergistic effect that could be beneficial for treating AML with MLL rearrangements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of Decitabine in Combination with Arsenic Trioxide on Prolife-ration and Apoptosis of Human Acute Myeloid Leukemia MV4-11 Cells]. Chen, SS., Zhao, YP., Wu, WZ., et al.[2018]

In a study of 62 patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), those who received the monoclonal antibody gemtuzumab ozogamicin (GO) prior to stem cell transplantation had a significantly higher risk of developing venoocclusive disease (VOD), with 64% of GO-exposed patients affected compared to only 8% of those without GO exposure.

The study found that the timing of stem cell transplantation after GO administration is critical; 90% of patients who underwent transplantation within 3.5 months of receiving GO developed VOD, highlighting the importance of monitoring and timing in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Wadleigh, M., Richardson, PG., Zahrieh, D., et al.[2022]

Gemtuzumab ozogamicin (GO) combined with cytarabine showed promising results in two pediatric patients with relapsed acute myeloid leukemia (AML), significantly reducing minimal residual disease to unprecedented levels.

The treatment had a relatively mild toxicity profile, although it did cause severe but manageable myelosuppression, indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular response in two children with relapsed acute myeloid leukemia treated with a combination of gemtuzumab ozogamicin and cytarabine. Brethon, B., Auvrignon, A., Cayuela, JM., et al.[2019]

Inqovi, a combination of decitabine and cedazuridine, was approved by the FDA for treating myelodysplastic syndromes (MDS) based on a phase III study involving 133 adults, showing similar effectiveness to intravenous decitabine.

The treatment demonstrated a complete remission rate of 21% in one study and 18% in another, with a median duration of remission lasting around 7.5 to 8.7 months, while adverse reactions were consistent with those seen in IV decitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. Kim, N., Norsworthy, KJ., Subramaniam, S., et al.[2023]

Cytarabine and thioguanine therapy successfully achieved complete remission of acute myelocytic leukemia in a 22-year-old pregnant woman, demonstrating their efficacy in treating this type of leukemia.

The treatment was initiated during the 26th week of pregnancy and resulted in the delivery of a healthy infant without chromosomal abnormalities, suggesting that this therapy can be safely administered to pregnant patients after the first trimester.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute leukemia during pregnancy. Raich, PC., Curet, LB.[2019]

In a Phase II trial involving 35 elderly patients (ages 51 to 80) with acute myelogenous leukemia (AML), a new chemotherapy regimen (V-TAD) achieved a complete remission rate of 42%, with a median remission duration of 6 months.

Despite being tolerated well, the V-TAD regimen did not improve overall survival rates compared to previous treatments, largely due to a high rate of resistant and recurrent leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of acute myelogenous leukemia in patients over 50 years of age with V-TAD: a Southwest Oncology Group study. Bigelow, CL., Kopecky, K., Files, JC., et al.[2019]

Gemtuzumab ozogamicin (GO) combined with standard-dose cytarabine shows promise for treating newly diagnosed acute myeloid leukemia (AML) in elderly patients, with preliminary results indicating its effectiveness, especially in patients with favorable and intermediate cytogenetic risk.

The combination of GO with high-dose cytarabine has been found to be safe and more effective for treating refractory AML compared to previous treatments, and initial data suggest that allogeneic stem cell transplantation is feasible after GO therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin (mylotarg) for the treatment of acute myeloid leukemia--ongoing trials. Gleissner, B., Schlenk, R., Bornhäuser, M., et al.[2019]

In a phase I study involving 20 adult patients with relapsed or refractory acute myeloid leukemia (AML), the combination of clofarabine and gemtuzumab ozogamicin (GO) showed an overall response rate of 42%, indicating potential effectiveness in this difficult-to-treat population.

The maximum tolerated dose (MTD) of clofarabine was determined to be 20 mg/m², but the high rate of dose-limiting toxicities (38%) such as prolonged myelosuppression and hepatotoxicity suggests that further studies should explore lower doses of GO to improve safety while preserving efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study of clofarabine in combination with fractionated gemtuzumab ozogamicin in patients with refractory or relapsed acute myeloid leukemia. Foster, MC., Amin, C., Voorhees, PM., et al.[2019]

Oral azacitidine (CC-486) has been shown to improve overall survival as maintenance therapy for older patients with acute myeloid leukemia who are in complete remission, highlighting its efficacy in this specific patient population.

The combination of decitabine and cedazuridine (ASTX727) is approved for treating adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia, particularly those with intermediate-1 or higher risk, indicating its targeted therapeutic application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The path to approval for oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes. Kipp, D., H Wei, A.[2022]

Thioguanine was tested as a primary therapy in seven patients with chronic granulocytic leukaemia (C.G.L.), but it did not lead to prolonged remission or conversion to Philadelphia chromosome negativity in any patient.

Despite inducing neutropenia in some cases, thioguanine was found to be at least as effective as busulphan for initial treatment and offered the benefit of quick recovery from blood cell suppression when treatment was stopped, suggesting it deserves further study for managing C.G.L. in its chronic phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thioguanine as primary treatment for chronic granulocytic leukaemia. Spiers, AS., Galton, DA., Kaur, J., et al.[2019]

In a study of 90 patients with acute myeloid leukemia (AML) in first relapse, combining gemtuzumab ozogamycin (GO) with intermediate- to high-dose cytarabine (IHDAraC) resulted in a significantly higher response rate (68% vs 45%) and improved overall survival (median 35 months vs 6 months) compared to IHDAraC alone.

The benefits of the IHDAraC + GO combination were particularly evident in patients with low- or intermediate-risk cytogenetics, suggesting that this treatment strategy could be more effective for these specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved outcome of patients with low- and intermediate-risk cytogenetics acute myeloid leukemia (AML) in first relapse with gemtuzumab and cytarabine versus cytarabine: results of a retrospective comparative study. Prebet, T., Etienne, A., Devillier, R., et al.[2019]

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]

Citations

1. everyone.org everyone.org/explore/compare?id1=49&id2=352

Besponsa (inotuzumab ozogamicin) vs Inqovi (decitabine ... The results from the INO-VATE ALL study provided strong evidence for the efficacy of Besponsa in the targeted patient population with relapsed or refractory B- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12548704/

A tour of leukemia progress in 2025, viewed through the MD ... Advances in the prognostication, monitoring, and treatment of both the acute and chronic leukemias have led to drastically improved outcomes ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06351306?term=AREA%5BInterventionSearch%5D(tabloid)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=1

NCT06351306 | DEC-C and Thioguanine for R/R AML The purpose of this study is to find out if oral decitabine-cedazuridine (Inqovi®) is effective, safe, and able to be tolerated without severe side effects ...

4. withpower.com withpower.com/trial/phase-2-leukemia-myeloid-acute-2024-86c49

DEC-C + Thioguanine for AML · Info for Participants The purpose of this study is to find out if oral decitabine-cedazuridine (Inqovi®) is effective, safe, and able to be tolerated without severe side effects ...

5. ashpublications.org ashpublications.org/ashclinicalnews/news/5344/In-Oral-Maintenance-Therapy-in-AML-Do-All-Roads

In Oral Maintenance Therapy in AML, Do All Roads Lead to ... CC-486 did improve median OS and median relapse-free survival compared with placebo, but in the end, "All roads lead to Rome."

6. ashpublications.org ashpublications.org/blood/article/143/1/11/498663/How-I-treat-refractory-and-relapsed-acute-myeloid

How I treat refractory and relapsed acute myeloid leukemia Among patients who received intensive therapy, the outcome is especially poor for those with a cytogenetic risk that is not favorable, FLT3 with ...