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Relapsed/Refractory Acute Myeloid LeukemiaPhase 1NCT06549790

Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia

A Phase 1 study testing NMS-03597812 in people with Relapsed/Refractory Acute Myeloid Leukemia, run by Nerviano Medical Sciences at 7 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
NMS-03597812
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
7 sitesUnited States
Study dates
16 Oct 2024to 15 May 2030
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of refractory/relapsed (R/R) AML according to 2022 ELN recommendation:
  • Phase Ia
  • single agent dose escalation of NMS-03597812: R/R AML patients who have exhausted standard therapy: a) prior fit patients to intensive chemotherapy (IC): failed at least one cycle of IC in front-line therapy or b) prior unfit to IC: failed at least 2 cycles of hypomethylating agents (HMA)/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; c) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
  • Phase Ib
  • Cohort A: single agent in R/R AML TP53mt patients who have exhausted standard therapy: a) prior unfit to intensive chemotherapy (IC): failed at least 2 cycles of HMA/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; b) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
  • Cohort B: single agent in R/R AML TP53wt patients who have exhausted standard therapy: a) prior fit patients to intensive chemotherapy (IC): failed at least one cycle of IC in front-line therapy or b) prior unfit to IC: failed at least 2 cycles of HMA/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; c) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
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  • Adult (age ≥ 18 years) patients
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Unless agreed with sponsor, the interval from prior antitumor treatment should be at least 2 weeks or 5 half-lives, whichever is longer, other than hydroxyurea
  • All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 5.0 Grade≤ 1
  • Adequate organ function
  • Must use highly effective contraception or true abstinence. Female patients must be surgically sterile or, if patient is of childbearing potential, must agree to use effective contraception of therapy and in the following 210 days after discontinuation of study treatment. Since NMS-03597812 has potential induction of CYP3A4, women of childbearing potential must be advised that hormonal contraceptives might lose efficacy and must use alternate form of highly effective contraception. Male patients must be surgically sterile or must agree to use highly effective contraception or true abstinence during the period of therapy and in the following 120 days for male patients who must refrain from donating sperm during this period after discontinuation of study treatment.
  • Capability to swallow capsules intact (without chewing, crushing, or opening)
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures
  • Signed and dated Independent Ethics Committee (IEC) or Institutional Review Board (IRB)-approved informed consent form indicating that the patient is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the investigational nature of the therapy, potential benefits, side effects, discomforts, risks, and alternative treatments.

Who cannot join

  • Current enrollment in another interventional clinical study unless only participating in survival follow up
  • White blood cells (WBC) count >20×10^3/microliter (μL). However, patients can be treated with hydroxyurea and/or leukapheresis prior to study treatment start to reduce the WBC to ≤ 20×10^3/μL to enable eligibility for study drug dosing.
  • Diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia
  • Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or cone biopsied in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
  • Patients with known leukemia involvement of central nervous system (CNS).
  • Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment start and/or persistent non- hematologic toxicities of Grade ≥2 related to the transplant
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  • Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
  • Patients with QTcF interval ≥ 470 milliseconds or with risk factors for torsade de pointes (e.g., uncontrolled heart failure, uncontrolled hypokalemia, history of prolonged QTc interval or family history of long QT syndrome). For patients receiving treatment with concomitant medications known to prolong the QTc interval, replacement with another treatment needs to be considered. If replacement or discontinuation is not clinically feasible, a careful risk/benefit evaluation should be performed prior to enrollment.
  • Pregnancy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the screening period prior to start of study drug.
  • Breast-feeding or planning to breast feed during the study or within 90 days after study treatment.
  • Known active gastrointestinal disease (eg, gastro-duodenal ulcer, gastrectomy, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
  • Patient who are receiving concomitant medications with antacids (proton pump inhibitors are strictly prohibited; calcium carbonate antacids are only allowed 6 hours prior to a dose or 1 hour after). Note: exclusion criterion not applicable to optional backfill cohort for investigation of drug-drug interaction with antiacids.
  • Patient who are receiving concomitant medications that are strong inducers or inhibitors of CYP3A4 (with the exception of azole antifungals) and CYP2C9 that cannot be replaced with alternative therapy.
  • Patients who are receiving concomitant medications that are sensitive substrates of CYP3A4,CYP2D6, CYP1A2 and CYP2B6 with narrow therapeutic window that cannot be replaced with alternative therapy. Drugs with broad therapeutic indices may still be acceptable.
  • Patients who are receiving concomitant medications that are strong or moderate P-gp inhibitors that cannot be replaced with alternative therapy.
  • Major surgery within 4 weeks before study treatment start.
  • Radiotherapy within 4 weeks before study treatment start. However, if the radiation portal covered ≤5 % of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy.
  • History of necrotic pancreatitis or acute severe pancreatitis, requiring medical intervention and/or hospitalization, in the previous 6 months before study treatment start.
  • NOTE: Other protocol defined inclusion/exclusion criteria may apply.

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Alberto Ocana contact

+39 0331-581111

clinicaltrials@nervianoms.com

7 sites in 1 country

United States7 sites, 6 recruiting

  • Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

    Recruiting

  • Rocky Mountain Cancer Centers

    Aurora, Colorado, 80012

    Recruiting

  • Gabrail Cancer Research Center

    Canton, Ohio, 44718

    Recruiting

  • City of Hope - Duarte

    Duarte, California, 91010

    Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • Medical Oncology Hematology Consultants

    Newark, Delaware, 19713

    Recruiting

  • Mayo Clinic Cancer Center (MCCC) - Rochester

    Rochester, Minnesota, 55905

    Withdrawn

Other trials in United States

About this study

Official title: A Phase Ia/Ib Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia Including Patients With TP53 Mutations

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.

Being tested
NMS-03597812
Keywords
Leukemia, Relapsed/Refractory Acute Myeloid Leukemia, TP53 mutations
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NMS-03597812Drug

    Route of Administration: Oral

Study groups in NCT06549790
Study groupRoleWhat they receive
NMS-03597812ExperimentalDose 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.
Receives: Drug: NMS-03597812

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase Ia (escalation) - Number of Participants with Adverse Events (AEs)

    Evaluation of AE frequency and severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0), including dose limiting toxicities (DLTs), laboratory measurements, electrocardiogram (ECG) measurements, vital sign measurements

    Measured: Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 13 months)

  2. Phase Ib (expansion) - Complete Remission (CR) rate

    Complete Remission (CR) rate, as defined by the Investigators based on the 2022 European LeukemiaNet (ELN) recommendations

    Measured: From date of treatment initiation up to hematological relapse (Approximately 12 months)

Secondary outcomes (22)

  1. Phase Ia - Complete remission (CR) rate

    Complete Remission (CR) rate, as defined by the Investigators based on the 2022 European LeukemiaNet (ELN) recommendations.

    Measured: From date of treatment initiation up to hematological relapse (Approximately 12 months)

  2. Phase Ia - Maximum concentration (Cmax) of NMS-0597812

    Plasma samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  3. Phase Ia - Related time of achievement of occurrence of Cmax (tmax) of NMS-0597812

    Plasma samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  4. Trough concentration (Cτ) area under concentration versus time up to 24 hours (dosing interval) of NMS-0597812

    Plasma samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  5. Phase Ia - Half-life of the terminal phase (t½,z) of NMS-0597812

    Plasma samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  6. Phase Ia - Plasma clearance (CL) of NMS-0597812

    Plasma samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  7. Phase Ia - Volume of distribution (Vss) of NMS-0597812

    Plasma samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  8. Phase Ia - Accumulation ratio (Rac) of NMS-0597812

    Plasma samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 15

  9. Phase Ia - Renal clearance (CLR) of NMS-03597812 excreted in urine (data permitting)

    Urine samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  10. Phase Ia - Cumulative amount recovered unchanged in the urine (Ae) of NMS-03597812 (data permitting)

    Urine samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  11. Phase Ia - Cumulative amount recovered unchanged in the urine expressed as a fraction of administered dose (Ae%) of NMS-03597812 (data permitting)

    Urine samples will be collected and used for pharmacokinetics assessments

    Measured: Cycle 1 (each cycle is 28 days): Day 1 and Day 15

  12. Phase Ib - Complete remission (CR) + complete remission with partial hematologic recovery (CRh) rate

    Number and percentage of patients who achieve CR and CRh as best response

    Measured: From date of treatment initiation up to hematological relapse (Approximately 12 months)

  13. Phase Ib - Complete remission (CR) + Complete remission with incomplete hematologic recovery (CRi) rate

    Number and percentage of patients who achieve CR and CRi as best response

    Measured: From date of treatment initiation up to hematological relapse (Approximately 12 months)

  14. Phase Ib - Complete remission (CR) + Complete remission with partial hematologic recovery (CRh) + complete remission with incomplete hematologic recovery (CRi) rate

    Number and percentage of patients who achieve CR, CRh and CRi as best response

    Measured: From date of treatment initiation up to hematological relapse (Approximately 12 months)

  15. Phase Ib - Overall Response Rate (ORR: CR + CRh + CRi + MLFS + PR)

    ORR: Complete remission (CR) + Complete remission with partial hematologic recovery (CRh) + Complete remission with incomplete hematologic recovery (CRi) + Morphological leukemia-free state (MLFS) + Partial remission (PR)

    Defined as the number and percentage of patients who achieve CR, CRh, CRi, MLFS and PR as best response in the analysis population

    Measured: From date of treatment initiation up to hematological relapse/progressive disease (Approximately 12 months)

  16. Phase Ib - Overall Survival (OS)

    Defined as the time from the date of start of treatment until the date of death from any cause. Patient who was not known to have died by the end of study will be censored at the date of last recorded date.

    Measured: First dose to the date of death from any cause or start of a new anti-cancer therapy, whichever comes first (Approximately 18 months)

  17. Phase Ib - Duration of Response (DoR)

    Defined as the time from the date of first response (CR, CRh, or CRi) until the date of documented hematologic relapse or death due to progression. DOR will be also calculated for overall response, including patients who achieve MLFS or PR as best response during the treatment.

    Measured: From the date of first response (CR, CRh, or CRi) to the date of hematological relapse or death due to progression, whichever comes first. (Approximately 12 months)

  18. Phase Ib - Event-Free Survival (EFS)

    Defined as the time from the date of treatment initiation to the date of hematological relapse from CR, CRh, or CRi, or death from any cause, whichever comes first.

    Measured: From the date of treatment initiation to the date of hematological relapse from CR, CRh, or CRi, date of treatment failure, or death from any cause, whichever comes first. (Approximately 18 months)

  19. Phase Ib - Relapse-free Survival (RFS)

    Measured only for patients achieving CR, CRh, or CRi, and it is defined as the time from the date of first achievement of remission until the date of hematologic relapse or death from any cause.

    Measured: Date of first achievement of remission until the date of hematologic relapse or death from any cause, whichever comes first (Approximately 12 months).

  20. Phase Ib - Proportion of patients bridged to hemopoietic stem cell transplantation (HSCT)

    Measured: From date of treatment initiation up to end of study (Approximately 18 months)

  21. Phase Ib - Rate of conversion from transfusion-dependence to transfusion independence

    Measured: From date of treatment initiation up to end of study (Approximately 18 months)

  22. Phase Ib - AE frequency and severity

    AE frequency and severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0), laboratory, ECG and vital sign measurements

    Measured: Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 13 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2024
  2. Study start16 Oct 2024
  3. Primary completion15 Sep 2029 (estimated)
  4. Study completion15 May 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
124 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06549790
Sponsor's protocol ID
PERKA-812-003
Status last verified
Oct 2025
First submitted
25 Jul 2024
Last updated
31 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NMS-03597812 in people with Relapsed/Refractory Acute Myeloid Leukemia, run by Nerviano Medical Sciences at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Alberto Ocana (+39 0331-581111, clinicaltrials@nervianoms.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase Ia (escalation) - Number of Participants with Adverse Events (AEs) (time frame: Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 13 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06549790.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2025.

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