Study of NMS-03592088 in Patients With Relapsed or Refrac... | NCT03922100

NCT03922100

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2018-002793-47	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
NMS-03592088	Experimental	Phase I Dose Escalation Schedule A - Starting dose of 20 mg/day Schedule B - Starting dose of 120 mg/day Only one dose level open for enrollment except EU backfill cohorts. Phase II Dose Expansion (Exploratory) - (EU) Recommended Phase II Dose (RP2D) of NMS-03592088 in Phase 1 Cohort 1: Patients who have failed standard of care including venetoclax and gilteritinib based therapies Cohort 2: Patients who have failed standard of care	Drug: NMS-03592088

Name	Type	Description	Arm Group Labels	Other Names
NMS-03592088	Drug	Route of administration: Oral	NMS-03592088

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase I - Number of Participants With Drug Related First-cycle Dose Limiting Toxicities (DLTs)	DLTs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.	From screening to end of first 28-days cycle (47 months)
Phase II - Number of Participants Who Achieved Composite Complete Remission (CRc) Rate i.e. Complete Remission (CR) + Complete Remission With Incomplete Hematologic Recovery (CRi).	CR = complete remission; CRc = composite complete remission rate; CRh = complete remission with partial hematologic recovery, CRi = complete remission with incomplete hematologic recovery; MLFS = morphologic leukemia free state; ORR = overall response rate; SD = stable disease Categories defined by the 2022 European LeukemiaNet (ELN) recommendations.	At Screening; Day 1 of Cycle 2 and Cycle 3; and Day 1 at subsequent even cycle; up to End of Treatment visit (within 7 days of the final dose of study drug), up to 17 months

Secondary Outcomes

Measure	Description	Time Frame
Treatment-emergent Adverse Events (TEAEs) Graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0 Criteria	TEAE with maximum Common Terminology Criteria (CTC) grade (graded by NCI CTCAE Version 5.0) experienced by each participant is presented. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented here. Phase 2 started before Phase 1 completed. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients with relapsed/refractory disease who have failed standard therapy or are unsuitable for standard treatment, with one the following confirmed diagnosis: AML as defined by the European LeukemiaNet (ELN)
Patients with confirmed diagnosis of AML as defined by the 2022 ELN recommendations
Patients must have failed standard of care.
Adult (age ≥ 18 years) patients
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
The interval from prior antitumor treatment to time of NMS-03592088 administration should be at least 2 weeks for any agents 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 hepatic and renal function
Patients must use highly effective contraception.
Signed and dated IEC or IRB-approved informed consent form.

Exclusion Criteria:

Current enrollment in another interventional clinical study
Diagnosis of acute promyelocytic leukemia or Breakpoint cluster region-Abelson (BCR-ABL)-positive leukaemia
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
Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
Patients with QTcF interval ≥ 480 milliseconds or with risk factors for torsade de pointes
Pregnancy.
Breast-feeding or planning to breast feed during the study or within 3 months after study treatment.
Any of the following in the previous 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis
Known active, life threatening or clinically significant uncontrolled systemic infection.
Known active gastrointestinal disease
Known active gastrointestinal ulcer
Other severe or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
Known diagnosis of myasthenia gravis

US only:

Signs or symptoms of myasthenia gravis or stroke during screening
Patients with myasthenia gravis specific autoantibodies or any known history of myasthenia gravis (MG) autoantibodies at screening window
Concomitant medications with the potential to cause de novo myasthenia gravis, worsening of myasthenia gravis or cause myasthenia gravis-like symptoms
Uncontrolled hypertension, atrial fibrillation or flutter, ventricular arrhythmia or receiving treatment for cardiac rhythm disorder or diabetes that is not adequately controlled

Other protocol specific inclusion/exclusion criteria may apply

Contacts/Locations Module

Name	Affiliation	Role
Alessandro Rambaldi, MD	ASST Papa Giovanni XXIII	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Centre Hospitalier du Mans		Le Mans		72037	France
Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hotel-Dieu

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	Phase 1, Schedule A: 20 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 20 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.
FG001	Phase 1, Schedule A: 40 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 40 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.
FG002	Phase 1, Schedule A: 80 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 80 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.
FG003	Phase 1, Schedule A: 120 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.
FG004	Phase 1, Schedule A: 180 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
FG005	Phase 1, Schedule A: 270 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 270 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
FG006	Phase 1, Schedule A: 300 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 300 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
FG007	Phase 1, Schedule A: 360 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 360 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle
FG008	Phase 1, Schedule B: 120 mg	All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 28 consecutive days, in a 28-day cycle
FG009	Phase 1, Schedule B: 180 mg	All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 28 consecutive days, in a 28-day cycle.
FG010	Phase 1, Schedule B: 250 mg	All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 250 mg administered orally once daily for 28 consecutive days, in a 28-day cycle
FG011	Phase 2, Schedule B, Cohort 1:360+150 mg	Participants who had failed standard of care including Venetoclax and Gilteritining based therapies. NMS-03592088 was administered, on Cycle 1, at 360 mg/day (loading dose) for 5 consecutive days, followed by 150 mg/day (maintenance dose) for 23 consecutive days. The same maintenance dose (150 mg/day) was administered from Cycle 2 onwards.
FG012	Phase 2, Schedule B, Cohort 2:360+150 mg	Participants who had failed standard of care. NMS-03592088 was administered, on Cycle 1, at 360 mg/day (loading dose) for 5 consecutive days, followed by 150 mg/day (maintenance dose) for 23 consecutive days. The same maintenance dose (150 mg/day) was administered from Cycle 2 onwards.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG0043 subjects FG0054 subjects FG00610 subjects FG0073 subjects FG0084 subjects FG0096 subjects FG0104 subjects FG0115 subjects FG01210 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0003 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG004

Type	Comment	Reasons
Death		FG0000 subjects FG0011 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase 1, Schedule A: 20 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 20 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.
BG001	Phase 1, Schedule A: 40 mg

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase I - Number of Participants With Drug Related First-cycle Dose Limiting Toxicities (DLTs)

DLTs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Participants evaluable for determination of DLT: For each schedule and dose level tested, this population included all participants enrolled in the dose escalation part who received at least 70% of the study drug in the first cycle, unless the reason for non-compliance was drug-related toxicity, and for whom a DLT assessment was available within the DLT window. In case the participant did not fulfill 1 or more of the aforementioned criteria, he/she was to be replaced.

Posted

Count of Participants

Participants

From screening to end of first 28-days cycle (47 months)

ID	Title	Description
OG000	Phase 1, Schedule A: 20 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 20 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1, Schedule A: 20 mg	All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 20 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Lisa Mahnke	Nerviano Medical Sciences S.r.l.	+39 0331-581111		clinicaltrials@nervianoms.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 28, 2024	Jun 10, 2025	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Mar 28, 2024	Jun 10, 2025	SAP_001.pdf

Submission Tracking

Condition Browse Module

ID	Term
D015470	Leukemia, Myeloid, Acute
D015477	Leukemia, Myelomonocytic, Chronic

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

EG0000 events0 affected3 at risk

EG0010 events0 affected3 at risk

EG0020 events0 affected3 at risk

EG0030 events0 affected3 at risk

EG0040 events0 affected3 at risk

EG0050 events0 affected4 at risk

EG0062 events2 affected10 at risk

EG0070 events0 affected3 at risk

EG0080 events0 affected4 at risk

EG0092 events2 affected6 at risk

EG0101 events1 affected4 at risk

EG0114 events4 affected15 at risk

EG0002 events1 affected3 at risk

EG0010 events0 affected3 at risk

EG00214 events3 affected3 at risk

EG0034 events1 affected3 at risk

EG0044 events1 affected3 at risk

EG0059 events2 affected4 at risk

EG0062 events2 affected10 at risk

EG0072 events1 affected3 at risk

EG0080 events0 affected4 at risk

EG0092 events2 affected6 at risk

EG0100 events0 affected4 at risk

EG0110 events0 affected15 at risk

OG003NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG004NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG005NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG006NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG007NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG008NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG009NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG010NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG011NA± NALast sampling time was 24 hrs after dosing on day 1 \& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.

OG011NA± NAThe half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated