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

NCT05601726 | Recruiting Phase 1

• 1 other identifier: ABD3001CLIN1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Acute Myeloid Leukemia, Adult; Myelodysplastic Syndromes

Keywords

Acute Myeloid Leukemia, Adult; Myelodysplastic syndromes; First in Human; ABD-3001

Outcome Measures

Primary Outcomes (2)

• SAD : Estimation of the Maximum Tolerated Dose (MTD) of ABD-3001 as well as the doses and frequencies to be explored during the MAD

  The primary endpoint is to assess the recommended dose range to be tested during the MAD by evaluation of incidence of patients who experienced Dose Limiting Toxicities (DLTs). according to CTCAE v5.0. The recommendation for doses to be tested during the MAD will be determined using all available data, which will include Dose Limiting Toxicities (DLTs), MTD if it has been reached, and other toxicities, signs of anti-leukemic activity, pharmacokinetic and pharmacodynamic characteristics.

  7 days for SAD part

• MAD : To evaluate the safety, tolerability and to define a recommended dose range for further trials.

  To assess the impact of ABD-3001 on safety and on its tolerability by evaluating: 1. Incidence of Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0 Nov. 27, 2017)), timing, seriousness, and relationship to ABD-3001 either observed by the investigator during physical examination, or reported spontaneously by the patient, 2. Incidence of laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0 Nov. 27, 2017), and timing.

  3 months for MAD part.

Secondary Outcomes (15)

• SAD : To evaluate the overall safety and tolerability profile of ABD-3001

  7 days for SAD part

• SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001

  7 days for SAD part

• SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001

  7 days for SAD part

• SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001

  7 days for SAD part

• SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001

  7 days for SAD part

Study Arms (2)

Single Administration Dose (SAD) of ABD-3001

EXPERIMENTAL

Dose escalation of 6 doses level using a 3+3 design.

Drug: ABD-3001

Multiple Administration Dose (MAD) of ABD-3001

EXPERIMENTAL

3 doses regimens in parallel during 3 cycles of 28 days

Drug: ABD-3001

Interventions

ABD-3001 DRUG

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.

Also known as: DIMATE

Single Administration Dose (SAD) of ABD-3001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Advanced BioDesign: lead

Study Sites (3)

Hôpital de la Timone

Marseille, France, 13005, France

RECRUITING

Hôpital Saint-Louis

Paris, France, 75475, France

RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, France, 69495, France

RECRUITING

Related Publications (1)

• Venton G, Colle J, Tichadou A, Quessada J, Baier C, Labiad Y, Perez M, De Lassus L, Loosveld M, Arnoux I, Abbou N, Ceylan I, Martin G, Costello R. Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients. J Cell Mol Med. 2024 Oct;28(19):e70011. doi: 10.1111/jcmm.70011.

  PMID: 39392121 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

dimethylthioampal

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Laurent BASSET

  Advanced BioDesign

  STUDY DIRECTOR

Central Study Contacts

Guillaume MARTIN

CONTACT

+33 (4) 82 53 89 62; guillaume.martin@a-biodesign.com

Laurent BASSET

CONTACT

+33 (0)4 28 29 46 78; laurent.basset@a-biodesign.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: November 1, 2022
• Study Start: November 8, 2022
• Primary Completion: June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)