NMS-03597812 for AML

Recruiting at 5 trial locations

Overseen By Salvatore Marengoni Galdy

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nerviano Medical Sciences

Must not be taking: Antacids, CYP3A4 inducers

Disqualifiers: Active second malignancy, CNS leukemia, others

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

Compensation: Varies

Number of Visits: 2

124 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of PERKA-812-003 study is to investigate the safety, pharmacokinetics and preliminary anti-tumor activity of treatment with NMS-03597812 as single agent in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) patients who have exhausted standard treatment, including a subset of patients with TP53 mutations. It is anticipated that combination with venetoclax will be further evaluated following a future protocol amendment, once the Recommended Range Dose (RDR) as single agent has been defined.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, especially those that affect specific enzymes (like CYP3A4) or prolong the QTc interval, unless they can be replaced with alternatives. You should discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the drug NMS-03597812 for AML?

Research shows that drugs targeting the FLT3 gene, which is mutated in about 30% of AML patients, can potentially improve treatment outcomes. FLT3 inhibitors, like midostaurin and gilteritinib, have shown promise in treating AML, suggesting that similar drugs might also be effective. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with Acute Myeloid Leukemia (AML) that has come back or didn't respond to standard treatments. It's also looking at a subgroup of these patients who have specific genetic changes called TP53 mutations.

Inclusion Criteria

I am willing and able to follow the study's schedule and procedures.

I haven't had cancer treatment for at least 2 weeks or 5 half-lives, except for hydroxyurea.

Signed and dated Independent Ethics Committee (IEC) or Institutional Review Board (IRB)-approved informed consent form

Exclusion Criteria

Patients with QTcF interval ≥ 470 milliseconds or with risk factors for torsade de pointes

I am taking medications that are sensitive to certain enzymes.

I have a digestive system disease that affects food absorption.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment Phase Ia (Dose Escalation)

Participants receive NMS-03597812 orally once daily in repeated 4-week cycles to determine the Recommended Range Dose (RDR)

28 days per cycle, multiple cycles

Cycle 1: Day 1 and Day 15 visits (in-person)

Treatment Phase Ib (Dose Expansion)

Dose expansion in cohorts A and B to evaluate NMS-03597812 in specific patient subgroups

12 months

Regular visits throughout treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

28-day follow-up after end of treatment

Treatment Details

Interventions

• NMS-03597812

Trial Overview The study tests NMS-03597812, a new potential treatment for AML. Initially, it's given alone to determine safety and dosage; later, it may be combined with another drug called venetoclax after further review.

Participant Groups

Group I: NMS-03597812 Experimental Treatment 1 Intervention

Dose escalation (Phase Ia): Administered orally once daily (28 consecutive days) in repeated 4-week cycles. Each cycle is 28 days. Expansion cohorts (Phase Ib, Cohorts A and B): The dose expansion may comprise up to a total of 2 single arms of NMS-03597812 as single agent: * Cohort A: in patients with TP53mt relapsed/refractory acute myeloid leukemia (R/R AML) prior unfit to intensive chemotherapy (IC) who have exhausted standard treatment options * Cohort B: in prior fit or unfit patients to IC with TP53wt R/R AML who have exhausted standard treatment options Backfill cohorts: Optional backfill cohorts may be opened at any time during the conduct of the trial to further evaluate the following items: NMS-03597812 dosing alone, pharmacokinetic (PK), drug-drug interactions, food effects, biomarkers and QTc for NMS-03597812 as single agent.

Who Is Running the Clinical Trial?

Nerviano Medical Sciences

Lead Sponsor

Trials

14

Recruited

770+

Findings from Research

Recent advancements in treatments for acute myeloid leukemia (AML), including new drugs like midostaurin and venetoclax, have improved post-remission therapy options for both younger and older patients, changing the approach to consolidation therapy.

The measurement of measurable residual disease (MRD) is now being used to tailor treatment plans, helping to determine the best duration and type of therapy, as well as the timing for allogeneic hematopoietic cell transplantation (allo-HCT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Induction Treatment for Acute Myeloid Leukemia: Something Change? Jaramillo, S., Schlenk, RF.[2023]

Next generation sequencing (NGS) has significantly advanced the understanding of acute myeloid leukemia (AML) by identifying genetic mutations and precursor lesions, which are now influencing treatment decisions and patient stratification.

The integration of genetic profiling into clinical practice is expected to enhance diagnosis, risk assessment, and the development of personalized treatment plans, including the use of recently approved drugs targeting specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation Sequencing in AML-On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation? Leisch, M., Jansko, B., Zaborsky, N., et al.[2020]

Glasdegib, a smoothened (SMO) inhibitor, has been approved by the FDA and EMA for treating naïve acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy, showing efficacy in controlling the disease when combined with low-dose cytarabine.

Clinical studies indicate that glasdegib has a favorable safety profile and may enhance the effectiveness of both traditional chemotherapy and biological treatments, such as FLT3 inhibitors, although further research is needed to identify which patients will benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glasdegib for the treatment of acute myeloid leukemia. Bruzzese, A., Martino, EA., Labanca, C., et al.[2023]

In a study of 75 newly diagnosed acute myeloid leukaemia (AML) patients, those with FLT3 mutations had a complete remission rate of 69.2% after standard induction chemotherapy, which is slightly lower than the 77.4% rate in FLT3-negative patients.

Despite the presence of FLT3 mutations, there were no significant differences in overall survival or relapse rates between FLT3-positive and FLT3-negative groups, suggesting that FLT3 status may not be a determining factor in treatment outcomes for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Patients with FLT3 Positive Acute Myeloid Leukaemia; an Experience from a Tertiary Care Hospital in Karachi, Pakistan. Zulfiqar, M., Ali, N., Shaikh, U., et al.[2023]

Approximately 30% of adult patients with acute myeloid leukemia (AML) have mutations in the FLT3 gene, which significantly worsen their prognosis, highlighting the importance of genetic testing in treatment planning.

Targeting FLT3 with investigational therapies could transform AML treatment by specifically inhibiting the growth of cancer cells while sparing normal cells, paving the way for more personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FLT3 inhibitors in the treatment of acute myeloid leukemia: the start of an era? Pemmaraju, N., Kantarjian, H., Ravandi, F., et al.[2021]

References

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

Post-Induction Treatment for Acute Myeloid Leukemia: Something Change? [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Next Generation Sequencing in AML-On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation? [2020]

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

Glasdegib for the treatment of acute myeloid leukemia. [2023]

4. Pakistan pubmed.ncbi.nlm.nih.gov

Outcomes of Patients with FLT3 Positive Acute Myeloid Leukaemia; an Experience from a Tertiary Care Hospital in Karachi, Pakistan. [2023]

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

FLT3 inhibitors in the treatment of acute myeloid leukemia: the start of an era? [2021]