Decitabine for Myelofibrosis

Not currently recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, Antiretrovirals

Disqualifiers: CNS disease, Uncontrolled illness, HIV, 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

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

Compensation: Varies

Number of Visits: 12

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of decitabine for individuals with myelofibrosis, a type of blood cancer that causes scar tissue in the bone marrow. The goal is to determine if decitabine can block certain proteins that deactivate important genes involved in this cancer. Individuals with myelofibrosis who have anemia (low red blood cells) or an enlarged spleen, and have not previously tried decitabine, might be suitable candidates. Participants will receive decitabine in cycles, with treatment continuing unless the disease worsens or side effects become too severe. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that decitabine is likely to be safe for humans?

Research has shown that decitabine, a drug used to treat myelofibrosis, has been tested for safety in other studies. In one study, 21 patients received low doses of decitabine injected under the skin, and the treatment was generally well-tolerated. Importantly, severe side effects were not commonly reported, although some unexpected side effects did occur during treatment.

Overall, decitabine is considered a useful treatment option for similar conditions, like serious blood disorders, and has been used in various medical settings. This suggests that while some side effects may occur, the treatment is generally safe, especially when other treatments fail. Discussing potential risks and benefits with a healthcare provider is always important before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelofibrosis?

Decitabine is unique because it offers a new approach to treating myelofibrosis. Unlike traditional treatments that mainly focus on managing symptoms or modifying other pathways, decitabine is a hypomethylating agent. It works by altering the expression of genes involved in cell growth, which can potentially halt or reverse disease progression. Researchers are excited about this treatment because it’s administered subcutaneously, which could improve patient comfort and compliance compared to intravenous options.

What evidence suggests that decitabine might be an effective treatment for myelofibrosis?

Research has shown that decitabine might help treat myelofibrosis, a type of blood cancer. One study found that a low-dose injection of decitabine under the skin had a 33% success rate in patients with myelofibrosis, meaning about one-third of the patients responded positively to the treatment. The positive effects lasted an average of seven months, with some patients responding for less time and others for more. Decitabine blocks proteins that can turn off certain genes in cancer cells, potentially stopping the cancer from growing. These findings suggest that decitabine, which participants in this trial will receive, could be a promising option for people with advanced myelofibrosis, especially if other treatments haven't worked. ^{1 4 6 7 8}

Who Is on the Research Team?

Olatoyosi M. Odenike

Principal Investigator

University of Chicago Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11599980/

A multicenter phase 2 clinical trial of low-dose subcutaneous ... The overall response rate for low-dose subcutaneous decitabine was 33% in this prospective clinical trial of 21 patients with myelofibrosis.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024001824

Oral Decitabine/Cedazuridine Is an Effective Ambulatory ... Outcomes are dismal for patients with myelofibrosis (MF) who are no longer responsive to JAK2 inhibitors (JAKi) and/or have increasing blast cell numbers.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38839448/

Oral Decitabine/Cedazuridine Is an Effective Ambulatory ... Background: Outcomes are dismal for patients with myelofibrosis (MF) who are no longer responsive to JAK2 inhibitors (JAKi) and/or have increasing blast cell ...

4. curetoday.com curetoday.com/view/subcutaneous-dacogen-elicits-responses-among-some-with-myelofibrosis

Subcutaneous Dacogen Elicits Responses Among Some ... A 10-day low-dose Dacogen regimen showed a 33% response rate in myelofibrosis patients, with a median response duration of seven months. · High ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00095784

Decitabine in Treating Patients With Myelofibrosis 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04657081

Study Details | NCT04657081 | Pharmacokinetics, Safety, ... Decitabine 5-day cumulative AUC in Phase 1. Cycle 2 (28 days per cycle). Safety: Participants with TEAEs, Number of participants with treatment-emergent adverse ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4546869/

Therapeutic benefit of decitabine, a hypomethylating agent ... Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00630994

NCT00630994 | Low-Dose Decitabine in Treating Patients ... PURPOSE: This phase II trial is studying the side effects and how well low-dose decitabine works in treating patients with symptomatic myelofibrosis. Detailed ...