search
Back to results

Escalation of Doses of Daratumumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients of 60 Years Old or More With Adverse Risk Acute Myeloblastic Leukemia (AML) (DARALAM) (DARALAM)

Primary Purpose

Adult Patients With Adverse Risk Acute Myeloblastic Leukemia

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Darzalex
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Patients With Adverse Risk Acute Myeloblastic Leukemia

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age >= 60 ans Poor prognosis AML defined according to the following criteria:1. For first-line AML:intermediate or unfavorable risk according to ELN 2017 2.for Relapsed AML:regardless of the ELN risk group ECOG <= 2 Patient eligible for intensive chemotherapy Who provide their written informed consent Liver workup: transaminases < 3x normal, bilirubin < 1.5 X normal Creatinine clearance > 60ml/mn LVEF >= 50%. Exclusion Criteria: Patients with FLT3 ITD or TKD mutation Patients with tuberculosis Patients with documented active infection with COVID 19 Patients with hereditary fructose intolerance (HFI) Uncontrolled infection Active or past infection with Hep B, C or HIV+ Not Affiliated with French social security system or no beneficiary from such system Pregnant women or patients who cannot take contraception ( contraceptive pill, abstinence, unauthorised IUD) in case of fertility. A patient who cannot continue contraception for at least 6 months after the last injection of DARATUMUMAB is not eligible for inclusion. Breastfeeding women Minors Adults under guardianship, curatorship or safeguard of justice Hypersensitivity to any of the active ingredients or excipients Patients with significant cardiovascular pathology including any of the following: myocardial infarction within 6 months prior to study entry, unstabilized coronary artery disease, uncontrolled hypertension, congestive heart failure. Patient with disease requiring systemic immunosuppressive therapy (such as high-dose steroids defined as ≥ 10mg prednisone or equivalent per day) within 4 weeks prior to the 1st scheduled dose of study treatment with the exception of dermocorticoids

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Darzalex

    Arm Description

    DARZALEX® Dose level 1 : 1800 mg Day 1 Dose level 2 : 1800 mg Day 1 and 8 (+/- 2 days) Dose level 3 : 1800 mg à Day 1, 8 (+/- 2 days) and D15 (+/- 2 days)

    Outcomes

    Primary Outcome Measures

    DLT
    Dose at which no toxic effect is observed, by determination of the LDT (Toxic Limit Dose). A TLD is defined by the occurrence of grade ≥ 3 daratumumab related toxicity that is not reversible after 7 days (except for haematological toxicity) or the absence of emergence from aplasia at D45 of induction (in the absence of treatment failure). Toxicity is assessed according to NCI-CTCAE version 5 criteria. The search for DLT is continued until D45 of induction.

    Secondary Outcome Measures

    response to the induction treatment
    calculation of the rate of complete remission (CR) with negative residual disease (CR MRD-), CR, CR with incomplete haematological recovery (CRi), MLFS (morphological leukemia free state), partial response (PR) or treatment failure according to the 2017 NLE definition between D30 and D45.
    Assessment of myelotoxicity
    Neutrophil recovery time (>1.0 × 109/L) from D1 - Recovery time of platelets (>100 × 109/L) from D1
    Overall survival (OS)
    time from D1 of induction to date of last contact or death
    Event-free survival (EFS)
    time from D1 of induction to date of relapse, death or date of last
    Relapse incidence
    Flow cytometry (FCM) investigation of myeloid-derived suppressor cells
    Comparison of MDSC values in CMF
    research on the level of CD38 expression on blasts

    Full Information

    First Posted
    February 13, 2023
    Last Updated
    February 27, 2023
    Sponsor
    Nantes University Hospital
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05749276
    Brief Title
    Escalation of Doses of Daratumumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients of 60 Years Old or More With Adverse Risk Acute Myeloblastic Leukemia (AML) (DARALAM)
    Acronym
    DARALAM
    Official Title
    Multicentric Phase 1 Study With Escalation of Doses of Daratumumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients of 60 Years Old or More With Adverse Risk Acute Myeloblastic Leukemia (AML) (DARALAM)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    May 2023 (Anticipated)
    Primary Completion Date
    November 2025 (Anticipated)
    Study Completion Date
    November 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Nantes University Hospital

    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
    To search for a Maximum Tolerated Dose (MTD) for the combination of daratumumab and induction chemotherapy with Idarubicin and cytarabine in patients with Acute Myeloblastic Leukemia (AML) of poor prognosis

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Adult Patients With Adverse Risk Acute Myeloblastic Leukemia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Model Description
    Continual Reassessment Method for MTD
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    12 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Darzalex
    Arm Type
    Experimental
    Arm Description
    DARZALEX® Dose level 1 : 1800 mg Day 1 Dose level 2 : 1800 mg Day 1 and 8 (+/- 2 days) Dose level 3 : 1800 mg à Day 1, 8 (+/- 2 days) and D15 (+/- 2 days)
    Intervention Type
    Drug
    Intervention Name(s)
    Darzalex
    Intervention Description
    DARZALEX® = Daratumumab. Solution for injection, 1800 mg/15 mL, single vial. Sub-cutaneous administration. Dose level 1 : 1800 mg Day 1 Dose level 2 : 1800 mg Day 1 and 8 (+/- 2 days) Dose level 3 : 1800 mg à Day 1, 8 (+/- 2 days) and D15 (+/- 2 days)
    Primary Outcome Measure Information:
    Title
    DLT
    Description
    Dose at which no toxic effect is observed, by determination of the LDT (Toxic Limit Dose). A TLD is defined by the occurrence of grade ≥ 3 daratumumab related toxicity that is not reversible after 7 days (except for haematological toxicity) or the absence of emergence from aplasia at D45 of induction (in the absence of treatment failure). Toxicity is assessed according to NCI-CTCAE version 5 criteria. The search for DLT is continued until D45 of induction.
    Time Frame
    DAY 45
    Secondary Outcome Measure Information:
    Title
    response to the induction treatment
    Description
    calculation of the rate of complete remission (CR) with negative residual disease (CR MRD-), CR, CR with incomplete haematological recovery (CRi), MLFS (morphological leukemia free state), partial response (PR) or treatment failure according to the 2017 NLE definition between D30 and D45.
    Time Frame
    DAY 45
    Title
    Assessment of myelotoxicity
    Description
    Neutrophil recovery time (>1.0 × 109/L) from D1 - Recovery time of platelets (>100 × 109/L) from D1
    Time Frame
    Day 1
    Title
    Overall survival (OS)
    Description
    time from D1 of induction to date of last contact or death
    Time Frame
    6 months
    Title
    Event-free survival (EFS)
    Description
    time from D1 of induction to date of relapse, death or date of last
    Time Frame
    6 months
    Title
    Relapse incidence
    Time Frame
    6 months
    Title
    Flow cytometry (FCM) investigation of myeloid-derived suppressor cells
    Time Frame
    Day 45
    Title
    Comparison of MDSC values in CMF
    Time Frame
    Day 45
    Title
    research on the level of CD38 expression on blasts
    Time Frame
    Day 1

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age >= 60 ans Poor prognosis AML defined according to the following criteria:1. For first-line AML:intermediate or unfavorable risk according to ELN 2017 2.for Relapsed AML:regardless of the ELN risk group ECOG <= 2 Patient eligible for intensive chemotherapy Who provide their written informed consent Liver workup: transaminases < 3x normal, bilirubin < 1.5 X normal Creatinine clearance > 60ml/mn LVEF >= 50%. Exclusion Criteria: Patients with FLT3 ITD or TKD mutation Patients with tuberculosis Patients with documented active infection with COVID 19 Patients with hereditary fructose intolerance (HFI) Uncontrolled infection Active or past infection with Hep B, C or HIV+ Not Affiliated with French social security system or no beneficiary from such system Pregnant women or patients who cannot take contraception ( contraceptive pill, abstinence, unauthorised IUD) in case of fertility. A patient who cannot continue contraception for at least 6 months after the last injection of DARATUMUMAB is not eligible for inclusion. Breastfeeding women Minors Adults under guardianship, curatorship or safeguard of justice Hypersensitivity to any of the active ingredients or excipients Patients with significant cardiovascular pathology including any of the following: myocardial infarction within 6 months prior to study entry, unstabilized coronary artery disease, uncontrolled hypertension, congestive heart failure. Patient with disease requiring systemic immunosuppressive therapy (such as high-dose steroids defined as ≥ 10mg prednisone or equivalent per day) within 4 weeks prior to the 1st scheduled dose of study treatment with the exception of dermocorticoids
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    PIERRE PETERLIN
    Phone
    02 40 08 32 71
    Email
    Pierre.PETERLIN@chu-nantes.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MATHILDE HUNAULT
    Organizational Affiliation
    University Hospital, Angers
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    MARC BERNARD
    Organizational Affiliation
    CHU Rennes
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Escalation of Doses of Daratumumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients of 60 Years Old or More With Adverse Risk Acute Myeloblastic Leukemia (AML) (DARALAM)

    We'll reach out to this number within 24 hrs