Clinical Trials /

Study of Escalating Doses of INA03 Administered Intravenously as Single Agent in Adult Patients With Relapse/Refractory Acute Leukemia

NCT03957915

Description:

This Phase 1 Study is an open-label, non-randomized, dose escalation, safety, efficacy, pharmacokinetic, and pharmacodynamic evaluation study of INA03 administered as a single agent IV infusion every 2 weeks to patients ≥18 years of age with R/R AML, MLL, or ALL. The study will be performed in 2 parts: a Dose Titration for Day 1 study (Part 1) followed by a Dose Escalation Part (Part 2) of INA03 used as monotherapy.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Mixed Phenotype Acute Leukemia
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Escalating Doses of INA03 Administered Intravenously as Single Agent in Adult Patients With Relapse/Refractory Acute Leukemia
  • Official Title: A Phase I, First in Human, Open-label Study of Escalating Doses of INA03 Administered Intravenously as Single Agent in Adult Patients With Relapse/Refractory Acute Leukemia

Clinical Trial IDs

  • ORG STUDY ID: INA03-IPC 2018-008
  • SECONDARY ID: 2019-000814-13
  • NCT ID: NCT03957915

Conditions

  • Acute Lymphoblastic Leukemia Recurrent
  • Acute Lymphoblastic Leukemia, in Relapse
  • Acute Myeloid Leukemia, in Relapse
  • Acute Myeloid Leukaemia Recurrent
  • Mixed Phenotype Acute Leukemia

Interventions

DrugSynonymsArms
INA03 administrationINA03

Purpose

This Phase 1 Study is an open-label, non-randomized, dose escalation, safety, efficacy, pharmacokinetic, and pharmacodynamic evaluation study of INA03 administered as a single agent IV infusion every 2 weeks to patients ≥18 years of age with R/R AML, MLL, or ALL. The study will be performed in 2 parts: a Dose Titration for Day 1 study (Part 1) followed by a Dose Escalation Part (Part 2) of INA03 used as monotherapy.

Detailed Description

      This Phase 1 Study is an open-label, non-randomized, dose escalation, safety, efficacy,
      pharmacokinetic, and pharmacodynamic evaluation study of INA03 administered as a single agent
      IV infusion every 2 weeks to patients ≥18 years of age with R/R AML, MLL, or ALL.

      The study will be performed in 2 parts: a Dose Titration for Day 1 study (Part 1) followed by
      a Dose Escalation Part (Part 2) of INA03 used as monotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
INA03ExperimentalINA03 administration
  • INA03 administration

Eligibility Criteria

        Inclusion Criteria:

        . Patient with

          -  cytologically confirmed and documented B-cell or T-cell ALL or de novo, secondary or
             therapy-related AML or Mixed Phenotype Acute Leukemia (MPAL) defined according to
             World Health Organization (WHO) 2016 classification28 AND

          -  with 20% or more CD71 positive blast cells

          -  in relapse after- or refractory to registered therapies or ineligible to standard
             treatments

          -  with circulating blasts ≤ 20 000/mm3. For eligible patients with AML/ALL with blasts >
             20000/mm3, a treatment with hydroxyurea is allowed to maintain tumor cells ≤ 20000/mm3
             2. Male or female age ≥ 18 years 3. WHO performance status 0-2 4. Following laboratory
             values unless considered due to the leukemia:

               1. AST and or ALT ≤ 2.5 ULN

               2. Total bilirubin level < 1.5 ULN (except Gilbert disease)

               3. Serum creatinine ≤ 1.5 ULN

               4. LDH < 3-5 ULN

               5. Uric acid ≤8 mg/dl

               6. Electrolyte panel within normal range

               7. Urine Dipstick Reading negative for proteinuria or, if documentation of +1
                  results for protein on dipstick reading, then total urinary protein ≤ 500 mg and
                  measured creatinine clearance ≥50mL/min/1.73m2 from a 24-hour urine collection

               8. Patients who have recovered at least CTCAE grade <2 5. Life expectancy greater
                  than 3 months 6. Women of child bearing potential must be willing to use birth
                  control method during the study duration (W4 or early termination) plus 30 days.
                  Male partner of women must use condom; in case of male patient, he must agree to
                  use condom during the study duration (W4 or early termination) plus 30 days; 7.
                  Pregnancy test (females of childbearing potential): negative 8. Signed informed
                  consent indicating that they have been informed of the procedures to be followed,
                  an is willing and able to comply the experimental nature of the therapy,
                  alternatives, potential benefits, side effects, risks, and discomforts 9. Patient
                  affiliated to the national "Social Security" regimen or beneficiary of this
                  regi-men

                  Exclusion Criteria:

                    1. Patients with acute promyelocytic leukemia

                    2. Patients with more than 30% marrow erythroid cells

                    3. Patients who have been treated with any anti-TfR antibody

                    4. Allogeneic stem cell transplantation in the last 6 months or with persistent
                       active GVHD. Autologous bone marrow transplant in the last 3 months

                    5. Last dose of prior chemotherapy, immunotherapy or investigational agent
                       within 14 days or within 5 half-lives before baseline receipt of study
                       medication, except for hydroxyurea and corticosteroids

                  7. Patients who have had a prior anaphylactic or other severe infusion reaction
                  such that the patient is unable to tolerate human immunoglobulin or monoclonal
                  antibody administration 8. Patients who have history or clinical evidence of
                  central nervous system (CNS), meningeal, or epidural disease from any cause
                  and/or peripheral neuropathy 9. Impaired cardiac function or clinically
                  significant cardiac disease, including any one of the following:

             a. New York Heart Association Class III or IV cardiac disease, including preexisting
             clinically significant arrhythmia, congestive heart failure, or cardiomyopathy b.
             Angina pectoris ≤ 3 months prior to starting study drug c. Acute myocardial infarction
             ≤ 3 months prior to starting study drug d. Other clinically significant heart disease
             (e.g., uncontrolled hypertension, history of labile hypertension, or history of poor
             compliance with an antihypertensive regimen) e. Left ventricular Ejection Fraction
             <45% 11. Uncontrolled infection 12. Acute and chronic liver disease 13. Other severe,
             acute, or chronic medical or psychiatric condition or laboratory abnor-mality that may
             increase the risk associated with study participation or study drug administra-tion or
             may interfere with the interpretation of study results and, in the judgment of the
             investigator, would make the subject inappropriate for this study.

             14. Patients with prior radiation therapy

               1. ≤12 weeks for cranial radiation therapy

               2. ≤ 4 weeks for wide field radiation therapy

               3. ≤2 weeks for involved field radiation therapy 15. Major surgery ≤ 4weeks prior to
                  starting study drug or who have not recovered from side effects of such therapy
                  16. Known diagnosis of HIV infection (HIV testing is not mandatory). 17. History
                  of another primary malignancy that is currently clinically significant or
                  currently requires active intervention 18. Pregnant or breastfeeding patient; 19.
                  Active drug or alcohol dependence; 20. Any psychological, familial, sociological
                  or geographical condition potentially hampering compliance with the study
                  protocol and follow-up schedule.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of the minimal erythroblastopenia-inducing dose (MEID) for INA03 in adults with refractory/relapsed acute leukemia
Time Frame:within 2 weeks from initial dosing
Safety Issue:
Description:MEID defined as the lowest dose associated with the risks of residual erythroblasts in the bone marrow at 2 weeks from initial dosing or grade 2 or above non hematologic toxicity within 2 weeks from initial dosing

Secondary Outcome Measures

Measure:Safety of INA03: NCI-CTCAE v5.0
Time Frame:Until 30 days after last dose
Safety Issue:
Description:Safety from the findings of reports of adverse events based on incidence, severity (as graded by the NCI-CTCAE v5.0), cumulative nature of treatment-emergent adverse event (TEAEs)
Measure:pharmacokinetic (PK) profile of INA03
Time Frame:From initial dosing day to Day 42
Safety Issue:
Description:Peak Plasma Concentration (Cmax) will be calculated, as appropriate
Measure:pharmacokinetic (PK) profile of INA03
Time Frame:From initial dosing day to Day 42
Safety Issue:
Description:Area under the plasma concentration versus time curve (AUC) will be calculated, as appropriate
Measure:pharmacokinetic (PK) profile of INA03
Time Frame:From initial dosing day to Day 42
Safety Issue:
Description:The terminal half-life will be calculated, as appropriate
Measure:pharmacodynamics (PD) profile of INA03
Time Frame:From screening to end of study visit (maximum 182 days)
Safety Issue:
Description:PD according to variation of erythroblast and blasts decrease using bone marrow as-pirate (BMA), and blood samples before and under treatment
Measure:Concentration of anti-INA03 antibodies
Time Frame:From screening to end of study visit (maximum 182 days)
Safety Issue:
Description:Serum concentration of anti-INA03 antibodies in micrograms per milliliter
Measure:Preliminary clinical response of INA03
Time Frame:from the date of treatment initiation (Day-1) to the date of relapse, progression or death, whichever comes first (a maximum 182 days)
Safety Issue:
Description:Clinical response as defined by European LeukemiaNet (ELN) 2017 recommendations

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Institut Paoli-Calmettes

Trial Keywords

  • acute leukemia
  • refractory
  • in relapse
  • antibody drug conjugate
  • first in human
  • escalating doses
  • INA03

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