Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNerviano Medical Sciences
About 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
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
Adult (age ≥ 18 years) patients
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
NMS-03597812
DrugRoute of Administration: Oral
Treatment groups
124 Participants
are divided into 1 treatment groupGroup A: NMS-03597812Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
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
Time frame
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
Time frame
From date of treatment initiation up to hematological relapse (Approximately 12 months)Secondary outcomes
1
Phase Ia - Complete remission (CR) rate
Complete Remission (CR) rate, as defined by the Investigators based on the 2022 European LeukemiaNet (ELN) recommendations.
Time frame
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
Time frame
Cycle 1 (each cycle is 28 days): Day 1 and Day 153
Phase Ia - Related time of achievement of occurrence of Cmax (tmax) of NMS-0597812
Plasma samples will be collected and used for pharmacokinetics assessments
Time frame
Cycle 1 (each cycle is 28 days): Day 1 and Day 154
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
Time frame
Cycle 1 (each cycle is 28 days): Day 1 and Day 15Sponsors and contacts
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Source ClinicalTrials.gov