NCT03008187: Diamond-01

MEN1703 (SEL24) in Participants With Acute Myeloid Leukemia

Completed Phase 1, PHASE2 Results posted Last updated 29 April 2025

What this trial tests

Phase 1, PHASE2 trial testing MEN1703 in Acute Myeloid Leukemia in 73 participants. Completed in 13 April 2023.

Timeline

10 March 2017

Primary endpoint
13 April 2023

13 April 2023

Quick facts

Lead sponsor	Menarini Group
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	73
Start date	10 March 2017
Primary completion	13 April 2023
Estimated completion	13 April 2023
Sites	15 locations across Italy, United States, Spain, Poland

Drugs / interventions tested

• MEN1703 — full drug profile →

Conditions studied

• Acute Myeloid Leukemia — all drugs for Acute Myeloid Leukemia →

Sponsor

Menarini Group — full company profile →

Who can join

18 and older, any sex, with Acute Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 1 and Part 2: Number of Participants Experiencing Treatment-emergent Adverse Events Primary · Up to 21 months

An adverse event (AE) was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the investigational medicinal product

Group	Value	95% CI
Cohort 1 (25 mg)	2
Cohort 2 (50 mg)	3
Cohort 3 (75 mg)	3
Cohort 4 (100 mg)	6
Cohort 5 (125 mg)	54
Cohort 6 (150 mg)	4

Part 1: Number of Participants Experiencing Dose-limiting Toxicity (DLT) Primary · Day 1 through Day 21 (first treatment cycle)

AEs were graded according to the National Cancer Institute common terminology criteria for adverse events, version 4.03. The following AEs were considered as DLT unless they were clearly and incontrovertibly attributable to the underlying disease or to an extraneous cause: Grade 5 toxicity; Grade 4 neutropenia lasting ≥42 days from the start of the therapy cycle in absence of evidence of active acute myeloid leukemia (AML) (\<5% blasts); Grade 3 or 4 non-hematologic toxicity (with protocol-define exceptions). Only clinically significant abnormalities in laboratory findings, physical examinatio

Group	Value	95% CI
Cohort 1 (25 mg)	1
Cohort 2 (50 mg)	0
Cohort 3 (75 mg)	0
Cohort 4 (100 mg)	0
Cohort 5 (125 mg)	1
Cohort 6 (150 mg)	3

Part 1 and Part 2: Overall Response Rate (ORR) Secondary · Up to 32 months

ORR was defined as the percentage of participants who had a complete remission (CR), complete remission with incomplete hematologic recovery (CRi), complete remission with partial hematologic recovery (CRh), or morphologic leukemia-free state (MLFS) response to therapy.

Group	Value	95% CI
Cohort 2 (50 mg)	0
Cohort 3 (75 mg)	50.0
Cohort 4 (100 mg)	0
Cohort 5 (125 mg)	13.5
Cohort 6 (150 mg)	0

Part 1 and Part 2: Partial Remission (PR) Rate Secondary · Up to 32 months

PR rate was defined as the percentage of participants who had a partial remission response to therapy.

Group	Value	95% CI
Cohort 2 (50 mg)	0
Cohort 3 (75 mg)	0
Cohort 4 (100 mg)	0
Cohort 5 (125 mg)	0
Cohort 6 (150 mg)	0

Part 1 and Part 2: Duration of Response (DoR) Secondary · Up to 32 months

DoR was defined as the time from the date of first CR, CRi, CRh, CR without minimal residual disease (CRMRD-), MLFS or PR until the date of documented relapse of any type, progressive disease or death due to disease progression for participants who achieve CR, CRi, CRh, CRMRD-, MLFS or PR. Results are reported in days.

Group	Value	95% CI
Cohort 2 (50 mg)	NA	NA – NA
Cohort 3 (75 mg)	79.0	NA – NA
Cohort 4 (100 mg)	NA	NA – NA
Cohort 5 (125 mg)	63.0	44.0 – NA
Cohort 6 (150 mg)	NA	NA – NA

Part 1 and Part 2: Relapse Free Survival (RFS) Secondary · Up to 32 months

RFS was defined as the time from the date of first CR, CRi, CRh, or CRMRD- until the date of documented relapse or death from any cause. Results are reported in days.

Group	Value	95% CI
Cohort 2 (50 mg)	NA	NA – NA
Cohort 3 (75 mg)	81.0	NA – NA
Cohort 4 (100 mg)	NA	NA – NA
Cohort 5 (125 mg)	64.0	44.0 – NA
Cohort 6 (150 mg)	NA	NA – NA

Part 1 and Part 2: Overall Survival (OS) Secondary · Up to 32 months

OS was defined as the number of days between the first study drug administration and death from any cause. Results are reported in days.

Group	Value	95% CI
Cohort 2 (50 mg)	43.0	NA – NA
Cohort 3 (75 mg)	138.5	63.0 – NA
Cohort 4 (100 mg)	NA	108.0 – NA
Cohort 5 (125 mg)	144.0	72.0 – 287.0
Cohort 6 (150 mg)	42.5	34.0 – NA

Part 1 and Part 2: Event Free Survival (EFS) Secondary · Up to 32 months

EFS was defined as the time from the date of first study drug intake until the date of documented relapse, treatment failure, or death from any cause. Results are reported in days.

Group	Value	95% CI
Cohort 2 (50 mg)	15.0	NA – NA
Cohort 3 (75 mg)	14.0	NA – NA
Cohort 4 (100 mg)	14.0	14.0 – NA
Cohort 5 (125 mg)	43.0	42.0 – 49.0
Cohort 6 (150 mg)	15.0	14.0 – NA

Part 1 and Part 2: Transfusion Conversion Rate Secondary · Up to 21 months

Transfusion conversion rate was defined as the percentage of participants who were transfusion dependent at baseline but became transfusion independent post-baseline. Participants were classified as baseline transfusion independent if there were no red blood cells (RBC) or platelet transfusions at baseline; otherwise, the participant was considered as baseline transfusion dependent. Participants were classified post-baseline transfusion independent in the event of 56 consecutive days without any RBC or platelet transfusion post-baseline; otherwise, the participant was considered post-baseline

Group	Value	95% CI
Cohort 5 (125 mg)	25

Part 1 and Part 2: Transfusion Maintenance Rate Secondary · Up to 21 months

Transfusion maintenance rate was defined as the percentage of participants who were transfusion independent at baseline and still maintained to be transfusion independent post-baseline. Participants were classified as baseline transfusion independent if there were no RBC or platelet transfusions at baseline; otherwise, the participant was considered as baseline transfusion dependent. Participants were classified post-baseline transfusion independent in the event of 56 consecutive days without any RBC or platelet transfusion post-baseline; otherwise, the participant was considered post-baseline

Group	Value	95% CI
Cohort 5 (125 mg)	100

Part 1 and Part 2: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Rate Secondary · Up to 21 months

Allogeneic HSCT rate was defined as the percentage of participants undergoing allogeneic stem cell transplant during the study period of each participant.

Group	Value	95% CI
Cohort 5 (125 mg)	2.7

Part 1 and Part 2: Percentage of Participants With ≥ 50% Bone Marrow Blast Reduction Secondary · Up to 20 months

Bone marrow aspirates/biopsies were taken at designated timepoints for evaluation of leukemic blast proportion in the bone marrow. A reduction in bone marrow blast proportion indicates increased anti-leukemic activity of the study drug.

Group	Value	95% CI
Cohort 2 (50 mg)	0
Cohort 3 (75 mg)	50.0
Cohort 4 (100 mg)	0
Cohort 5 (125 mg)	33.3
Cohort 6 (150 mg)	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were assessed up to 21 months. All-cause mortality, survival (RFS, EFS, OS), ORR, PR rate, and DOR were assessed up to 32 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 (25 mg)

Serious: 0/2 (0%)

Deaths: 2/2

Cohort 2 (50 mg)

Serious: 0/3 (0%)

Deaths: 3/3

Cohort 3 (75 mg)

Serious: 3/3 (100%)

Deaths: 3/3

Cohort 4 (100 mg)

Serious: 6/6 (100%)

Deaths: 1/6

Cohort 5 (125 mg)

Serious: 35/55 (64%)

Deaths: 35/55

Cohort 6 (150 mg)

Serious: 4/4 (100%)

Deaths: 4/4

Serious adverse events (52 terms)

Reaction	System	Cohort 1 (25 mg)	Cohort 2 (50 mg)	Cohort 3 (75 mg)	Cohort 4 (100 mg)	Cohort 5 (125 mg)	Cohort 6 (150 mg)
Pneumonia	Infections and infestations	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—
Pneumonia fungal	Infections and infestations	—	—	—	—	—	—
Intestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Anorectal infection	Infections and infestations	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—
Septic shock	Infections and infestations	—	—	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—	—	—	—
Atrial tachycardia	Cardiac disorders	—	—	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—	—	—	—
Hyphaema	Eye disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—	—
Gastric haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Odynophagia	Gastrointestinal disorders	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Multiple organ dysfunction syndrome	General disorders	—	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—	—
Drug-induced liver injury	Hepatobiliary disorders	—	—	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—	—	—

Other adverse events (223 terms — click to expand)

Reaction	System	Cohort 1 (25 mg)	Cohort 2 (50 mg)	Cohort 3 (75 mg)	Cohort 4 (100 mg)	Cohort 5 (125 mg)	Cohort 6 (150 mg)
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—	—
Activated partial thromboplastin time prolonged	Investigations	—	—	—	—	—	—
C-reactive protein increased	Investigations	—	—	—	—	—	—
Weight increased	Investigations	—	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Febrile neutropenia, Sepsis, Pneumonia fungal, Intestinal haemorrhage, Pyrexia, Anorectal infection, Cellulitis.

Data from ClinicalTrials.gov NCT03008187 adverse events section.

Sponsor's own description

The purpose of the clinical trial is to identify the maximum tolerated dose of MEN1703 and to further investigate its safety profile in participants with acute myeloid leukemia (AML).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Therapeutic targeting of "undruggable" MYC.
   Llombart V, Mansour MR. · · 2022 · cited 349× · PMID 34942444 · DOI 10.1016/j.ebiom.2021.103756
2. <i>FLT3</i> Mutations in Acute Myeloid Leukemia: Key Concepts and Emerging Controversies.
   Kennedy VE, Smith CC. · · 2020 · cited 132× · PMID 33425766 · DOI 10.3389/fonc.2020.612880
3. Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis.
   Yamashita M, Dellorusso PV, Olson OC, Passegué E. · · 2020 · cited 128× · PMID 32415283 · DOI 10.1038/s41568-020-0260-3
4. The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy.
   Yang Y, Zhang M, Wang Y. · · 2022 · cited 96× · PMID 39036551 · DOI 10.1016/j.jncc.2022.09.002
5. Rebelled epigenome: histone H3S10 phosphorylation and H3S10 kinases in cancer biology and therapy.
   Komar D, Juszczynski P. · · 2020 · cited 87× · PMID 33054831 · DOI 10.1186/s13148-020-00941-2
6. Emerging treatment paradigms with FLT3 inhibitors in acute myeloid leukemia.
   Short NJ, Kantarjian H, Ravandi F, Daver N. · · 2019 · cited 86× · PMID 30800259 · DOI 10.1177/2040620719827310
7. PIM kinase inhibition: co-targeted therapeutic approaches in prostate cancer.
   Luszczak S, Kumar C, Sathyadevan VK, Simpson BS, et al · · 2020 · cited 65× · PMID 32296034 · DOI 10.1038/s41392-020-0109-y
8. Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development.
   Stanchina M, Soong D, Zheng-Lin B, Watts JM, et al · · 2020 · cited 62× · PMID 33139625 · DOI 10.3390/cancers12113225