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)

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)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Adult Patients With Adverse Risk Acute Myeloblastic Leukemia
• Intervention / Treatment: Drug: Darzalex

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: PIERRE PETERLIN; Phone Number: 02 40 08 32 71; Email: Pierre.PETERLIN@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 2022 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darzalex; 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)	Drug: Darzalex; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	DAY 45

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of myelotoxicity	Neutrophil recovery time (>1.0 × 109/L) from D1 - Recovery time of platelets (>100 × 109/L) from D1	Day 1
Overall survival (OS)	time from D1 of induction to date of last contact or death	6 months
Event-free survival (EFS)	time from D1 of induction to date of relapse, death or date of last	6 months
Relapse incidence		6 months
Flow cytometry (FCM) investigation of myeloid-derived suppressor cells		Day 45
Comparison of MDSC values in CMF		Day 45
research on the level of CD38 expression on blasts		Day 1
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 2022 NLE definition between D30 and D45.	DAY 45

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: MATHILDE HUNAULT, University Hospital, Angers; Principal Investigator: MARC BERNARD, Chu Rennes

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: RC22_0372

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No