MEN1703 (SEL24) in Participants With Acute Myeloid Leukemia (Diamond-01)

A Phase I/II Study of SEL24 in Patients With Acute Myeloid Leukemia

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).

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: MEN1703

Detailed Description

Phase I/II, open-label, multi-center, dose escalation study to estimate the maximum tolerated dose of MEN1703 in participants with acute myeloid leukemia.

The clinical trial will investigate the safety profile and anti-leukemic activity of MEN1703 in participants with AML and that have no standard therapeutic options available.

The clinical trial encompasses 2 parts:

• Part 1: Ascending dose levels - the main purpose of this part of the clinical trial is to determine the highest dose of MEN1703 considered to be well tolerated.
• Part 2: Expansion cohort - the main purpose of this part of the clinical trial is to assess the safety and anti-leukemia activity of MEN1703 given at the highest tolerated dose in participant with relapsed/refractory acute myeloid leukemia, either all comers as well as harboring isocitrate dehydrogenase (IDH1/IDH2) mutations.

Participants participating to the clinical trial will take the study drug as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Italy
  • Meldola, Italy
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milano, Italy
    • Istituto Clinico Humanitas
  • Monza, Italy
    • ASST Monza - Ospedale San Gerardo
• Poland
  • Warsaw, Poland
    • Institute of Haematology and Blood Transfusion
  • Łódź, Poland
    • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi, Oddzial Hematologii z Pododdzialem Chemioterapi
• Spain
  • Badalona, Spain
    • Institut Catala d'Oncologia
  • Madrid, Spain
    • Hospital 12 de Octubre
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic, Taussig Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with diagnosis of AML, all comers or bearing IDH1 or IDH2 mutation (completed)
• Participant has no standard therapeutic options available and has either relapsed AML unsuitable for intensive chemotherapy, with no standard therapeutic options and/or not eligible for any approved targeted therapy or primary refractory AML unsuitable for intensive chemotherapy, with no standard therapeutic options and/or not eligible for any approved targeted therapy

Exclusion Criteria:

• Anti-cancer treatments (including cytotoxic chemotherapy, radiotherapy, hormonal therapy, biologic, immunotherapy or investigational drugs) received within 14 days or 5 half-lives for targeted therapies (whichever is shorter) before first dose of study drug (to be supplemented)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (25 mg); Participants received MEN1703 (25 milligrams [mg]) orally once daily for 14 consecutive days in cycles of 21 days.	Drug: MEN1703; MEN1703 given as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.; Other Names: SEL24-B489; SEL24
Experimental: Cohort 2 (50 mg); Participants received MEN1703 (50 mg) orally once daily for 14 consecutive days in cycles of 21 days.	Drug: MEN1703; MEN1703 given as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.; Other Names: SEL24-B489; SEL24
Experimental: Cohort 3 (75 mg); Participants received MEN1703 (75 mg) orally once daily for 14 consecutive days in cycles of 21 days.	Drug: MEN1703; MEN1703 given as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.; Other Names: SEL24-B489; SEL24
Experimental: Cohort 4 (100 mg); Participants received MEN1703 (100 mg) orally once daily for 14 consecutive days in cycles of 21 days.	Drug: MEN1703; MEN1703 given as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.; Other Names: SEL24-B489; SEL24
Experimental: Cohort 5 (125 mg); Participants received MEN1703 (125 mg) orally once daily for 14 consecutive days in cycles of 21 days.	Drug: MEN1703; MEN1703 given as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.; Other Names: SEL24-B489; SEL24
Experimental: Cohort 6 (150 mg); Participants received MEN1703 (150 mg) orally once daily for 14 consecutive days in cycles of 21 days.	Drug: MEN1703; MEN1703 given as oral capsules once daily for 14 consecutive days over a 21-day treatment cycle.; Other Names: SEL24-B489; SEL24

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Number of Participants Experiencing Treatment-emergent Adverse Events	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. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse events module.	Up to 21 months
Part 1: Number of Participants Experiencing Dose-limiting Toxicity (DLT)	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 examination, vital signs, weight, or electrocardiogram were considered for DLT assessment.	Day 1 through Day 21 (first treatment cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Overall Response Rate (ORR)	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.	Up to 32 months
Part 1 and Part 2: Partial Remission (PR) Rate	PR rate was defined as the percentage of participants who had a partial remission response to therapy.	Up to 32 months
Part 1 and Part 2: Duration of Response (DoR)	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.	Up to 32 months
Part 1 and Part 2: Relapse Free Survival (RFS)	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.	Up to 32 months
Part 1 and Part 2: Overall Survival (OS)	OS was defined as the number of days between the first study drug administration and death from any cause. Results are reported in days.	Up to 32 months
Part 1 and Part 2: Event Free Survival (EFS)	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.	Up to 32 months
Part 1 and Part 2: Transfusion Conversion Rate	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 transfusion dependent.	Up to 21 months
Part 1 and Part 2: Transfusion Maintenance Rate	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 transfusion dependent.	Up to 21 months
Part 1 and Part 2: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Rate	Allogeneic HSCT rate was defined as the percentage of participants undergoing allogeneic stem cell transplant during the study period of each participant.	Up to 21 months
Part 1 and Part 2: Percentage of Participants With ≥ 50% Bone Marrow Blast Reduction	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.	Up to 20 months
Part 1 and Part 2: Maximum Observed Concentration (Cmax) for MEN1703	Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. Results are reported as nanograms/milliliter (ng/mL). Standard error not reported, arithmetic coefficient of variation (CV%) reported instead.	Day 1 and Day 14 of Cycle 1 (pre-dose, up to 120 hours post dose) (21 days/cycle)
Part 1 and Part 2: Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for MEN1703	Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. AUClast was calculated by the linear trapezoidal rule. Results are reported in hour times nanograms/milliliter (h*ng/mL). Standard error not reported, arithmetic CV% reported instead.	Day 1 of Cycle 1 (pre-dose, up to 24 hours post dose) (21 days/cycle)
Part 1 and Part 2: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24) for MEN1703	Nominal blood samples were taken at designated timepoints for evaluation of concentration levels of MEN1703 in plasma. AUC0-24 was calculated by the linear trapezoidal rule. Results are reported in h*ng/mL. Standard error not reported, arithmetic CV% reported instead.	Day 14 of Cycle 1 (pre-dose, up to 120 hours post dose) (21 days/cycle)

Collaborators and Investigators

• Sponsor: Menarini Group
• Collaborators: Medpace, Inc.; Theradex
• Investigators: Principal Investigator: Farhad Ravandi, MD, Department of Leukemia, MDACC

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2017
• Primary Completion (Actual): April 13, 2023
• Study Completion (Actual): April 13, 2023

Study Registration Dates

• First Submitted: December 10, 2016
• First Submitted That Met QC Criteria: December 30, 2016
• First Posted (Estimated): January 2, 2017

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: AML; IDH; Relapsed/Refractory Acute Myeloid Leukemia
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: CLI24-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No