BMS-986253 for Myelodysplastic Syndrome

Overseen By Christine T McGowan

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: DNMTi

Must not be taking: ESAs, Lenalidomide, Luspatercept

Disqualifiers: Uncontrolled illness, Autoimmune, HIV, others

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

Compensation: Varies

Number of Visits: 4

Duration: 6 months

2 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for myelodysplastic syndromes (MDS), disorders affecting the bone marrow. The aim is to determine if the drug BMS-986253, used alone or with other medications, can be a safe and effective option for people with MDS. The trial includes different groups for patients with varying severity of the condition. It may suit adults diagnosed with MDS who experience issues like low blood cell counts or symptoms of anemia. Participants will receive the trial medication in cycles and undergo close monitoring for any changes in their condition. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in MDS treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational agents, you must stop them at least 28 days before starting the study treatment.

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

Research has shown that BMS-986253, a new drug tested for myelodysplastic syndromes (MDS), was safe in past studies. People with advanced solid tumors tolerated the drug well, suggesting it might also be safe for those with MDS.

Some trial participants will also receive decitabine and cedazuridine. These drugs already treat MDS and are generally considered safe, though some side effects have been reported. Previous research found that most patients experienced manageable side effects, which is encouraging for those considering joining the trial.

The trial is in its early stages, so researchers are still learning about the safety and effectiveness of these treatments for MDS. Participants will be closely monitored to ensure any side effects are quickly and effectively managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BMS-986253 because it targets interleukin 8 (IL-8), a protein associated with inflammation and tumor growth, offering a novel approach to treating myelodysplastic syndromes (MDS). Unlike the standard treatments like azacitidine and decitabine, which mainly focus on altering DNA methylation, BMS-986253 acts on a different pathway, potentially reducing disease progression more effectively. Additionally, when combined with DNA methyltransferase inhibitors, it could enhance the overall therapeutic effect, especially in higher-risk MDS patients. This unique mechanism of action sets it apart from existing therapies, providing new hope for patients with MDS.

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

Research shows that BMS-986253, a new treatment for myelodysplastic syndrome (MDS), might help patients by targeting interleukin 8 (IL-8), a protein involved in inflammation and the immune system, which plays a role in MDS. Early results from other conditions suggest it is generally safe. In this trial, some participants with higher-risk MDS may receive a combination of BMS-986253 with decitabine and cedazuridine, which has proven effective for MDS, with about 70% of patients showing positive results, such as improved blood cell counts. These findings suggest that both BMS-986253 and the decitabine and cedazuridine combination could effectively treat MDS. ^{1 2 4 6 7}

Who Is on the Research Team?

Najla El Jurdi, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults 18+ with Myelodysplastic Syndromes (MDS) who meet specific criteria, including having received certain prior treatments for MDS. They must have a life expectancy over 6 months and be able to perform daily activities with some degree of independence. Participants need proper liver and kidney function and cannot be pregnant or breastfeeding.

Inclusion Criteria

My liver and kidney functions meet the trial's requirements.

I can take care of myself but might not be able to do active work.

I have MDS with specific blood counts and have had certain treatments.

Exclusion Criteria

I do not have active or uncontrolled autoimmune diseases.

I do not have any unmanaged ongoing illnesses.

I have low platelet counts that don't respond to transfusions or dangerously low white blood cell counts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive BMS-986253 as an infusion on days 1 and 15 of each 28-day cycle, with some receiving additional DNMTi on days 2-6

6 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a follow-up visit 30 days after treatment ends and subsequent follow-ups via phone every 3-6 months

1 year

1 visit (in-person), phone follow-ups every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986253
• Decitabine and Cedazuridine

Trial Overview The trial is testing BMS-986253 alone or combined with decitabine and cedazuridine in treating MDS. It's given in cycles, with infusions on specific days, alongside oral medication for some participants. The goal is to see if this new drug combination is safe and effective against MDS.

How Is the Trial Designed?

Group I: Phase II Lower Risk (LR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 4 Interventions

Phase II dose of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) for lower risk (LR) myelodysplastic syndromes (MDS) participants.

Group II: Phase II Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 6 Interventions

Phase II dose of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) + deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for higher risk (HR) myelodysplastic syndromes (MDS) participants.

Group III: Phase I Lower Risk (LR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 4 Interventions

Escalating doses of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) for lower risk (LR) myelodysplastic syndromes (MDS) participants.

Group IV: Phase I Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants Experimental Treatment 6 Interventions

Escalating doses of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) + deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for higher risk (HR) myelodysplastic syndromes (MDS) participants.

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

In a study of 99 patients with myelodysplastic syndromes (MDS), decitabine administered at a higher dose of 20 mg/m² daily for 5 days every 4 weeks resulted in a 32% overall response rate, indicating significant efficacy in treating MDS.

The outpatient regimen of decitabine not only provided comparable efficacy to the FDA-approved inpatient schedule but also allowed for more than half of the patients to show clinical improvement, suggesting a safe and effective alternative treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. Steensma, DP., Baer, MR., Slack, JL., et al.[2023]

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]

Luspatercept has shown significant efficacy in treating low-risk myelodysplastic syndromes (MDS), with 63% of patients experiencing hematological improvement and 38% achieving transfusion independence in clinical trials.

Oral decitabine combined with oral cedazuridine has demonstrated pharmacological equivalence to intravenous decitabine, achieving overall response rates of 60% and 43% in phase 2 and 3 trials for high-risk MDS, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New treatment for myelodysplastic syndromes: luspatercept and oral hypomethylating agents]. Usuki, K.[2022]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

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 combination of oral cedazuridine and decitabine (C-DEC) has been shown to have a similar pharmacokinetic and pharmacodynamic profile to parenteral decitabine, making it a promising alternative for treating higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).

Phase 2 and phase 3 clinical trials confirmed the bioequivalence of C-DEC to parenteral decitabine, leading to FDA approval for its use in intermediate/high-risk MDS and CMML, highlighting its efficacy and safety as an oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies. Patel, AA., Cahill, K., Saygin, C., et al.[2023]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05148234

NCT05148234 | BMS-986253 in Myelodysplastic Syndromes BMS-986253 is a fully human Immunoglobulin G1 (IgG1) neutralizing antibody that showed a favorable safety profile in participants with advanced solid tumors.

2. withpower.com withpower.com/trial/phase-2-preleukemia-11-2021-0c45e

BMS-986253 for Myelodysplastic Syndrome The combination of decitabine and cedazuridine, part of the treatment, has been shown to be effective for myelodysplastic syndromes (MDS) with similar ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-13966

BMS-986253 in Myelodysplastic Syndromes - NCI Objective: To learn if HuMax-interleukin 8 (IL-8) BMS-986253 is a safe and effective treatment for MDS. Eligibility: Adults aged 18 and older with MDS.

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/34/NCT05148234/Prot_SAP_000.pdf

Abbreviated Title: BMS-986253 in MDS In this trial we hypothesize that the addition of BMS-986253 to treatment with DNMTi is safe in adult MDS participants. Based on the presented data on IL-8 in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10329313/

Role of innate immunological/inflammatory pathways in ... In this review we not only discuss the interplay of various innate immune pathways in MDS pathogenesis but also focus on potential therapeutic ...

6. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=000356-C&&query=Disease

NIH Clinical Center: Search the Studies To learn if BMS-986253 is a safe and effective treatment for MDS. Eligibility: Adults aged 18 and older with MDS. Design: Participants will be screened with ...

7. clin.larvol.com clin.larvol.com/trial/NCT05148234

BMS-986253 in Myelodysplastic Syndromes Complete Remission (CR) is bone marrow ≤55% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Partial Remission (PR) is ...