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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 (ODYSSEY)

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ClinicalTrials.gov Identifier: NCT05601726
Recruitment Status : Recruiting
First Posted : November 1, 2022
Last Update Posted : November 23, 2022
Sponsor:
Information provided by (Responsible Party):
Advanced BioDesign

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 followed by a "Regimen optimization" part with an extension cohort.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia, Adult Myelodysplastic Syndromes Drug: ABD-3001 Phase 1

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 followed by a "Regimen optimization" (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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-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 followed by a "Regimen optimization" part with an extension cohort.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: First-In-Human, Open Label, Dose Escalation Study to Evaluate Safety, PK and PD of ABD-3001 as Monotherapy in Relapsed/Refractory Acute Myeloid Leukemia or High/Very-high Risk Myelodysplastic Syndromes Patients, Ineligible for Intensive or New Generation Targeted Therapy.
Actual Study Start Date : November 8, 2022
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: Single Administration Dose (SAD) of ABD-3001
Dose escalation of 6 doses level using a 3+3 design.
Drug: ABD-3001
Each patient will receive a single and fixed 4 hours-intravenous infusion dose of ABD-3001. 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.
Other Name: DIMATE

Experimental: Multiple Administration Dose (MAD) of ABD-3001
Dose escalation of 3 doses level for a full cycle of treatment (28 days).
Drug: ABD-3001

Based on PK data gathered during the SAD, a dose regimen optimization will be done using population Pharmacokinetic modelling in order to set the optimal frequency of infusion per week to achieve sustained exposition throughout treatment period. Based on this analysis, the Sponsor will, in accordance with the Safety review Committee, define the occurrence of infusion to 1, 2 or 3 times per week, during 4 weeks (28 days ± 3 days).

Number of infusions given per week and dose increase between each dose will be set so that, whatever the initial dose used in the MAD part, total dose increase will never get above the MTD determined in the SAD part or a dose defined by the SRC, if no MTD is determined during the SAD part.

Other Name: DIMATE




Primary Outcome Measures :
  1. Estimation of the Maximum Tolerated Dose (MTD) [ Time Frame: 7 days for SAD part up to 2 months for MAD part. ]
    The primary endpoint is to assess the MTD by evaluation of incidence of patients who experienced Dose Limiting Toxicities (DLTs) assessed according to CTCAE v5.0.

  2. Recommendation of the dose for the Phase 2 (RP2D). [ Time Frame: 2 months for MAD part. ]
    The recommendation for the Phase 2 dose will be determined using MTD, cumulative safety and signs of anti-leukemic activity, pharmacokinetic and pharmacodynamic characteristics.


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 7 days for SAD part up to 2 months for MAD part. ]
    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. PK parameters assessment (Cmax) [ Time Frame: 7 days for SAD part up to 2 months for MAD part. ]
    Evaluation of maximum concentration (Cmax) of ABD-3001.

  3. PK parameters assessment (AUC) [ Time Frame: 7 days for SAD part up to 2 months for MAD part. ]
    Evaluation of Area Under the Curve (AUC) of ABD-3001.

  4. PK parameters assessment (Tmax) [ Time Frame: 7 days for SAD part up to 2 months for MAD part. ]
    Evaluation of time to maximum concentration (Tmax) of ABD-3001.

  5. PK parameters assessment (T1/2) [ Time Frame: 7 days for SAD part up to 2 months for MAD part. ]
    Evaluation of elimination half-life of ABD-3001.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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
  • 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
  • History of other malignancy in the last 12 months prior to study Visit 1
  • Other active solid tumor
  • Patients taking medications that are known to prolong the QT interval
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05601726


Contacts
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Contact: Guillaume MARTIN +33 (4) 82 53 89 62 guillaume.martin@a-biodesign.com
Contact: Laurent BASSET +33 (0)4 28 29 46 78 laurent.basset@a-biodesign.com

Locations
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France
Hôpital de la Timone Recruiting
Marseille, France, 13005
Contact: Régis COSTELLO       regis.costello@ap-hm.fr   
Hôpital Saint-Louis Not yet recruiting
Paris, France, 75475
Contact: Lina BENAJIBA       lina.benajiba@aphp.fr   
Centre Hospitalier Lyon Sud Not yet recruiting
Pierre-Bénite, France, 69495
Contact: Maël HEIBLIG       mael.heiblig@chu-lyon.fr   
Sponsors and Collaborators
Advanced BioDesign
Investigators
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Study Director: Laurent BASSET Advanced BioDesign
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Responsible Party: Advanced BioDesign
ClinicalTrials.gov Identifier: NCT05601726    
Other Study ID Numbers: ABD3001CLIN1
First Posted: November 1, 2022    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions