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)

NCT05749276 | Not Yet Recruiting Phase 1

• 1 other identifier: RC22_0372
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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

Conditions

Adult Patients With Adverse Risk Acute Myeloblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• response to the induction treatment

  DAY 45

• Assessment of myelotoxicity

  Day 1

• Overall survival (OS)

  6 months

• Event-free survival (EFS)

  6 months

• Relapse incidence

  6 months

Study Arms (1)

Darzalex

EXPERIMENTAL

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

Interventions

Darzalex DRUG

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)

Darzalex

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

MeSH Terms

Interventions

daratumumab

Study Officials

• MATHILDE HUNAULT

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

• MARC BERNARD

  CHU Rennes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

PIERRE PETERLIN

CONTACT

02 40 08 32 71; Pierre.PETERLIN@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Continual Reassessment Method for MTD

Study Record Dates

• First Submitted: February 13, 2023
• First Posted: March 1, 2023
• Study Start: May 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 18, 2024

Record last verified: 2024-04