First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult Patients

Trial Title: First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult Patients

NCT ID: NCT05601726

Condition: Acute Myeloid Leukemia, Adult
Myelodysplastic Syndromes

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome

Conditions: Keywords:
Acute Myeloid Leukemia, Adult
Myelodysplastic syndromes
First in Human
ABD-3001

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Sequential Assignment

Intervention model description: This First In Human (FIH) study is a prospective, open-label, multicenter, Phase 1 study, with a dose escalation design, followed by an optimized design. It will consist in a Single Ascending Dose (SAD) part and a Multiple Ascending Dose (MAD) part.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: ABD-3001
Description: Each patient will receive a fixed 4 hours-intravenous infusion dose of ABD-3001 once or twice a week. For SAD : The first dose of the first cohort will receive an estimated infusion dose of 18 mg/m² at Day 1. Subsequent cohorts will be given the following doses: 54 mg/m², 135 mg/m², 270 mg/m², 405 mg/m², 540 mg/m².
Arm group label: Single Administration Dose (SAD) of ABD-3001

Other name: DIMATE

Intervention type: Drug
Intervention name: ABD-3001
Description: For MAD : Based on all data gathered during the SAD including safety, PK and preliminary efficacy data, up to three doses were selected in accordance with the Safety review Committee (SRC). A dosage optimization analysis was performed at the end of the SAD cohort 6 using population pharmacokinetic modelling to set the optimal frequency of infusion per week for each selected dose to achieve sustained exposition throughout the treatment period. Based on this analysis, the Sponsor, in agreement with the SRC, defined 3 doses regimens that will be set up in parallel, with infusion of ABD-3001 once or twice a week during 3 cycles of 28 days.
Arm group label: Multiple Administration Dose (MAD) of ABD-3001

Other name: DIMATE

Summary: This First In Human (FIH) study is a prospective, open-label, multicenter, Phase 1 study, with a dose escalation design, followed by an optimized design. It will consist in a Single Ascending Dose (SAD) part and a Multiple Ascending Dose (MAD) part.

Detailed description: This FIH study combines, in patients with primary refractory or relapsed AML patients and in patients with high risk MDS a Single Ascending Dose (SAD) part (Part A) and a Multiple Ascending Dose (MAD) part (Part B). The objective of the SAD phase is to explore a wide range of dose administered as a single and fixed 4-hours intravenous infusion in order to select a dose and a dosing frequency (determined using pharmacokinetic and pharmacodynamics parameters). The objective of the MAD is to elucidate the pharmacokinetic (PK) and pharmacodynamics (PD) of multiple doses of ABD-3001. The dose levels and dosing intervals (i.e., time between consecutive doses) will be selected as those that are predicted to be safe from the SAD. Dose levels and dosing frequency will be derived from data obtained during the SAD.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Patients with relapsed/refractory Acute Myeloid Leukemia (AML) after failing at least one therapy regimen and a salvage treatment or are not eligible for salvage treatment regimens including targeted therapy - Patients with relapsed/refractory Myelodysplastic syndrome (MDS) ineligible for salvage treatment who are diagnosed high-risk and very high-risk using Revised International Prognostic Scoring System (IPSS-R) prognostic risk categorization - Patients not eligible to alloSCT - Negative blood or serum/urine pregnancy test Exclusion Criteria: - Patients with acute myeloid leukemia (AML) with Inv(16) MYH11-CBF-Beta or t(8;21) AML-ETO RUNX1-RUNX1 or (PML/RARA) karyotype abnormalities and eligible to targeted therapies - Participants with clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia - Ongoing immunosuppressive treatment - Hematopoietic stem cell transplantation (HSCT) performed within 3 months prior to study Visit 1 - Active infection requiring intravenous anti-infectious treatment during the screening period - Life-threatening illnesses other than the studied one, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety or interfere with the patient's ability to comply with the study activities - Anti-tumor therapy within 14 days of study Visit 1 - Prior participation in an interventional investigational clinical study (drug or medical device) within 21 days of study Visit 1 - Radiotherapy within 28 days prior to study Visit 1 - Current history of seropositivity to human immunodeficiency virus (HIV) or infection with active hepatitis C virus (HCV) or active hepatitis B virus (HBV) or active SARS-CoV-2 (Covid-19) or Syphilis, or Cytomegalovirus (CMV), or Epstein-Barr virus (EBV), or Human T-Lymphotropic Virus (HTLV1) - History of other malignancy in the last 12 months prior to study Visit 1 - Other active solid tumor - Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or Left Ventricular Ejection Fraction (LVEF) <50% attested by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days of C1D1 prior to study Visit 1 (Day 1, start of study therapy) - Subjects with a history of myocardial infarction within the last 3 months prior to study Visit 1 (Day 1, start of study therapy) - Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that increase the risk of QT prolongation or arrhythmic events - Major surgery within 4 weeks prior to study Visit 1 (Day 1, start of study therapy) - Any condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the clinical trial MAD specific exclusion criteria: Patients who have been part of SAD and have experienced a DLT.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Hôpital de la Timone

Address:
City: Marseille
Zip: 13005
Country: France

Status: Recruiting

Contact:
Last name: Régis COSTELLO
Email: regis.costello@ap-hm.fr

Facility:
Name: Hôpital Saint-Louis

Address:
City: Paris
Zip: 75475
Country: France

Status: Recruiting

Contact:
Last name: Lina BENAJIBA
Email: lina.benajiba@aphp.fr

Facility:
Name: Centre Hospitalier Lyon Sud

Address:
City: Pierre-Bénite
Zip: 69495
Country: France

Status: Recruiting

Contact:
Last name: Maël HEIBLIG
Email: mael.heiblig@chu-lyon.fr

Start date: November 8, 2022

Completion date: December 2026

Lead sponsor:
Agency: Advanced BioDesign
Agency class: Industry

Source: Advanced BioDesign

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05601726