Back to resultsFirst-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)
Primary Purpose
Acute Myeloid Leukemia, Adult, Myelodysplastic Syndromes
Status
Active
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
ABD-3001
ABD-3001
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia, Adult
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 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
Sites / Locations
- Hôpital de la Timone
- Hôpital Saint-Louis
- Centre Hospitalier Lyon Sud
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Single Administration Dose (SAD) of ABD-3001
Multiple Administration Dose (MAD) of ABD-3001
Arm Description
Dose escalation of 6 doses level using a 3+3 design.
Dose escalation of 3 doses level for a full cycle of treatment (28 days).
Outcomes
Primary Outcome Measures
Estimation of the Maximum Tolerated Dose (MTD)
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.
Recommendation of the dose for the Phase 2 (RP2D).
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
Adverse events
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.
PK parameters assessment (Cmax)
Evaluation of maximum concentration (Cmax) of ABD-3001.
PK parameters assessment (AUC)
Evaluation of Area Under the Curve (AUC) of ABD-3001.
PK parameters assessment (Tmax)
Evaluation of time to maximum concentration (Tmax) of ABD-3001.
PK parameters assessment (T1/2)
Evaluation of elimination half-life of ABD-3001.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05601726
Brief 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
Acronym
ODYSSEY
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.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 8, 2022 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Advanced BioDesign
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Adult, Myelodysplastic Syndromes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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)
Allocation
Non-Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Administration Dose (SAD) of ABD-3001
Arm Type
Experimental
Arm Description
Dose escalation of 6 doses level using a 3+3 design.
Arm Title
Multiple Administration Dose (MAD) of ABD-3001
Arm Type
Experimental
Arm Description
Dose escalation of 3 doses level for a full cycle of treatment (28 days).
Intervention Type
Drug
Intervention Name(s)
ABD-3001
Other Intervention Name(s)
DIMATE
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
ABD-3001
Other Intervention Name(s)
DIMATE
Intervention Description
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.
Primary Outcome Measure Information:
Title
Estimation of the Maximum Tolerated Dose (MTD)
Description
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.
Time Frame
7 days for SAD part up to 2 months for MAD part.
Title
Recommendation of the dose for the Phase 2 (RP2D).
Description
The recommendation for the Phase 2 dose will be determined using MTD, cumulative safety and signs of anti-leukemic activity, pharmacokinetic and pharmacodynamic characteristics.
Time Frame
2 months for MAD part.
Secondary Outcome Measure Information:
Title
Adverse events
Description
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.
Time Frame
7 days for SAD part up to 2 months for MAD part.
Title
PK parameters assessment (Cmax)
Description
Evaluation of maximum concentration (Cmax) of ABD-3001.
Time Frame
7 days for SAD part up to 2 months for MAD part.
Title
PK parameters assessment (AUC)
Description
Evaluation of Area Under the Curve (AUC) of ABD-3001.
Time Frame
7 days for SAD part up to 2 months for MAD part.
Title
PK parameters assessment (Tmax)
Description
Evaluation of time to maximum concentration (Tmax) of ABD-3001.
Time Frame
7 days for SAD part up to 2 months for MAD part.
Title
PK parameters assessment (T1/2)
Description
Evaluation of elimination half-life of ABD-3001.
Time Frame
7 days for SAD part up to 2 months for MAD part.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laurent BASSET
Organizational Affiliation
Advanced BioDesign
Official's Role
Study Director
Facility Information:
Facility Name
Hôpital de la Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Facility Name
Hôpital Saint-Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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