Decitabine for Myelofibrosis

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 36 weeks

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects and how well decitabine works in treating patients with myelofibrosis, a cancer of the blood system associated with fibrosis (scar tissue) in the bone marrow that is advanced and for which there is no standard therapy. Decitabine may block the actions of some proteins that are responsible for turning certain genes off in various cancers including myelofibrosis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiotherapy within 4 weeks before starting the study, and you cannot be on other investigational drugs.

What data supports the effectiveness of the drug Decitabine for Myelofibrosis?

Decitabine has shown promise in controlling disease and improving quality of life in a case of relapsed myelofibrosis after stem cell transplant, and it has been effective in treating acute myeloid leukemia by improving survival and response rates. ^{1 2 3 4 5}

Is Decitabine generally safe for human use?

Decitabine has been used in treating conditions like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and is generally well tolerated. Common side effects include fever, low platelet counts, and anemia, but it has relatively modest non-blood-related toxicity, making it a viable option for patients who cannot undergo more intensive treatments. ^{2 3 4 6 7}

How is the drug Decitabine unique for treating myelofibrosis?

Decitabine is unique because it is a DNA methyltransferase inhibitor, which means it works by altering the way genes are expressed in cells. This mechanism is different from many other treatments for myelofibrosis, which may focus on different pathways or symptoms. Additionally, when combined with cedazuridine, it can be taken orally, which is more convenient than intravenous administration. ^{2 3 8 9 10}

Research Team

Olatoyosi M. Odenike

Principal Investigator

University of Chicago Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with advanced myelofibrosis, a type of blood cancer. Eligible participants may have had previous treatments but not with decitabine. They should be in stable health otherwise, not pregnant or nursing, and willing to use contraception. Key criteria include specific diagnostic features of myelofibrosis, anemia or noticeable spleen enlargement.

Inclusion Criteria

I have anemia or an enlarged spleen.

My enlarged spleen's size has been measured with an ultrasound.

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

I have been treated with decitabine before.

I am HIV-positive and on combination anti-retroviral therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive decitabine subcutaneously on days 1-5 and 8-12, with treatment repeating every 42 days

36 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Decitabine

Trial Overview The trial is testing the effectiveness and side effects of decitabine in treating advanced myelofibrosis. Decitabine might block proteins that silence genes involved in this cancer's development. Participants will also undergo lab biomarker analysis to monitor responses.

Participant Groups

Group I: Treatment (decitabine) Experimental Treatment 2 Interventions

Patients receive decitabine SC on days 1-5 and 8-12. Treatment repeats every 42 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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 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 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]

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]

References

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

Improved donor chimerism in relapse myelofibrosis post allogenic stem cell transplant with azacitidine and oral decitabine-First case report. [2023]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Decitabine for acute myeloid leukemia. [2018]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Emerging targeted therapies in myelofibrosis. [2021]

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

Population Pharmacokinetic Analysis of Decitabine in Pediatric Patients With Acute Myeloid Leukemia. [2020]

7. China pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy of Low-Dose Decitabine alone for Treatment of Myelodysplastic Syndrome]. [2020]

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

Decitabine/Cedazuridine: First Approval. [2021]

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

Decitabine. MGI Pharma Inc/SuperGen Inc. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML. [2018]