Seclidemstat + Azacitidine for Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

Overseen By Guillermo M. Bravo

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP inhibitors, CYP inducers

Disqualifiers: Uncontrolled infection, Heart failure, Myocardial infarction, Long QT syndrome, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, seclidemstat (SP-2577) and azacitidine (Vidaza or 5-azacytidine), to determine the optimal dose and assess their effectiveness against certain blood cancers, specifically myelodysplastic syndrome and chronic myelomonocytic leukemia. Seclidemstat blocks certain enzymes to stop cancer cell growth, while azacitidine helps prevent growths that could become cancerous. This trial may suit individuals diagnosed with these specific blood conditions who have not responded well to previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically moderate or strong inhibitors or inducers of major CYP isoenzymes, 14 days before starting the trial. If you are on these medications, you will need to discuss with your doctor about stopping them.

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

Research has shown that combining seclidemstat with azacitidine may help treat certain blood conditions like myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). In earlier studies, this combination helped nearly half of the patients, with a 43% response rate, indicating some improvement. This suggests the treatment could be somewhat effective.

However, safety concerns exist. One study reported a serious side effect, which led to a temporary pause in the trial for a safety review. Participants should understand that while the treatment has shown some positive results, it also carries risks that require careful consideration. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of seclidemstat and azacitidine for treating myelodysplastic syndrome and chronic myelomonocytic leukemia because it offers a fresh angle on treatment. Unlike standard therapies like chemotherapy or single-agent hypomethylating agents, seclidemstat is a new type of drug that targets LSD1, an enzyme linked to cancer cell growth. This dual approach not only potentially enhances the effectiveness of azacitidine, a common treatment, but also opens up new possibilities for tackling these complex blood disorders. By combining these two drugs, researchers hope to improve outcomes for patients who have limited options with existing treatments.

What evidence suggests that this treatment might be an effective treatment for myelodysplastic syndrome or chronic myelomonocytic leukemia?

Research has shown that combining seclidemstat and azacitidine, the treatment under study in this trial, may effectively treat myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). Specifically, studies found that 43% of patients experienced a reduction in cancer activity, indicating nearly half of the patients responded positively to the treatment. This combination also improved survival rates compared to previous treatments for high-risk MDS and CMML. Seclidemstat blocks enzymes that cancer cells need to grow, while azacitidine helps prevent the growth of potential cancer cells. These findings suggest that using these two drugs together might be more effective than older treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Guillermo M. Bravo

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults diagnosed with myelodysplastic syndrome or chronic myelomonocytic leukemia, who haven't responded to certain treatments like azacitidine, can join this trial. They must understand the study and agree to participate, have proper kidney and liver function, an ECOG performance status of 0-2, and not be pregnant or breastfeeding. Those with uncontrolled infections, heart issues, or taking specific drugs that affect the trial medications are excluded.

Inclusion Criteria

Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study

My kidney function is within the normal range or slightly above.

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x ULN

Exclusion Criteria

I am not taking medications that are sensitive to changes by certain liver enzymes.

I do not have active hepatitis B, hepatitis C, or HIV.

I have had a heart attack in the last 6 months or have uncontrolled heart problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine IV or SC on days 1-7 and seclidemstat PO on a dose-escalation schedule. Cycles repeat every 28 days.

Up to 1 year

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days post-treatment, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Seclidemstat

Trial Overview The trial is testing the combination of seclidemstat and azacitidine to determine the best dose for treating certain blood cancers. Seclidemstat blocks enzymes needed for cancer cell growth while azacitidine may prevent cancerous growths from forming. The goal is to see if this combo kills more cancer cells.

How Is the Trial Designed?

Group I: Treatment (azacitidine, seclidemstat) Experimental Treatment 2 Interventions

Patients receive azacitidine IV over 10-40 minutes or SC on days 1-7. Patients also receive seclidemstat PO QD on day 1 of cycle 1 and PO BID on days 2-28 of cycle 1 and on days 1-28 of all subsequent cycles. There are 6 planned dose levels for seclidemstat: 300 mg, 450 mg, 600 mg, 900 mg, 1200 mg and 1500 mg. Successive cohorts of eligible patients will be treated with azacitidine. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza 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

In a real-life study of 49 patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), azacitidine demonstrated a clinically acceptable safety profile, with 67.3% of patients experiencing treatment-related adverse events.

Efficacy results showed that 41.4% of MDS and CMML patients achieved a complete or partial response, and 43.8% of transfusion-dependent patients became transfusion-independent, with a median overall survival of 490 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey. Beguin, Y., Selleslag, D., Meers, S., et al.[2015]

In a study of 149 patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), azacitidine treatment resulted in a median progression-free survival (PFS) of 10.9 months and an overall survival (OS) of 14.1 months, demonstrating its effectiveness in a real-world clinical setting.

The safety profile of azacitidine was consistent with previous clinical trials, and factors such as Eastern Cooperative Oncology Group (ECOG) performance status and red blood cell transfusion prior to treatment were identified as predictive factors for better PFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). Wehmeyer, J., Zaiss, M., Losem, C., et al.[2019]

In a study of 149 patients with high-risk myelodysplastic syndrome and acute myeloid leukemia, azacitidine (AZA) alone achieved a hematologic normalization (HN) rate of 32%, while the combination of AZA and entinostat resulted in a lower HN rate of 27%.

The addition of entinostat did not enhance the clinical response and was associated with less demethylation, indicating a potential antagonistic effect, while AZA alone showed promise with a median overall survival of 18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905. Prebet, T., Sun, Z., Figueroa, ME., et al.[2021]

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.

Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. Meers, S., Selleslag, D., Potier, H., et al.[2018]

In a study of 91 patients with chronic myelomonocytic leukemia (CMML) treated with azacitidine (AZA), the overall response rate was 58% between cycles 4 and 6, indicating that AZA is effective for this patient group.

Nearly half of the patients achieved transfusion independence, and one quarter experienced clinical benefits, suggesting that AZA can be a viable treatment option for various CMML subtypes, including those with lower-risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to azacitidine in patients with chronic myelomonocytic leukemia according to overlap myelodysplastic/myeloproliferative neoplasms criteria. Triguero, A., Xicoy, B., Zamora, L., et al.[2022]

Azacitidine has been shown to significantly prolong the time to progression to acute myeloid leukemia or death in myelodysplastic syndromes (MDS) patients, with a median time of 21 months compared to 13 months for supportive care in a study of 191 patients.

In a larger trial with 358 patients, azacitidine also significantly improved overall survival, extending it to 24.5 months compared to 15.0 months with conventional care, establishing it as a key first-line treatment for higher-risk MDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of azacitidine trials in Intermediate-2-and High-risk myelodysplastic syndromes. Fenaux, P., Ades, L.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04734990

NCT04734990 | Seclidemstat and Azacitidine for the ... This phase I/II trial identifies the best dose of seclidemstat when given together with azacitidine in treating patients with myelodysplastic syndrome or ...

2. onclive.com onclive.com/view/md-anderson-study-resumes-with-seclidemstat-azacitidine-in-mds-cmml

MD Anderson Study Resumes With Seclidemstat ... Interim results showed a 43% objective response rate and improved overall survival, surpassing historical outcomes in high-risk MDS and CMML ...

3. investors.salariuspharma.com investors.salariuspharma.com/news-releases/news-release-details/clinical-data-salarius-pharmaceuticals-seclidemstat-patients-mds

Clinical Data on Salarius Pharmaceuticals' Seclidemstat in ... Investigators reported a 43% overall response rate among 14 predominantly higher risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) ...

4. targetedonc.com targetedonc.com/view/fda-enforces-partial-hold-on-trial-of-seclidemstat-in-mds-cmml

FDA Enforces Partial Hold on Trial of Seclidemstat in MDS ... The FDA has placed a partial clinical hold on a phase 1 trial evaluating seclidemstat (SP-2577) when given in combination with azacitidine for the treatment of ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04734990

Seclidemstat and Azacitidine for the Treatment of ... The trial will be an open label, dose-finding, dose-expansion study to determine the maximum tolerated dose (MTD) and the safety and tolerability of ...

6. cancernetwork.com cancernetwork.com/view/fda-places-partial-hold-on-trial-for-seclidemstat-in-mds-cmml

FDA Places Partial Hold on Trial for Seclidemstat in MDS ... A serious grade 4 adverse effect reported in the phase 1/2 dose-escalation study evaluating seclidemstat combination therapy prompted the ...