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 Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| 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)
|
Outcome Measures
Primary Outcome Measures
- DLT [DAY 45]
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 [DAY 45]
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 [Day 1]
Neutrophil recovery time (>1.0 × 109/L) from D1 - Recovery time of platelets (>100 × 109/L) from D1
- Overall survival (OS) [6 months]
time from D1 of induction to date of last contact or death
- Event-free survival (EFS) [6 months]
time from D1 of induction to date of relapse, death or date of last
- 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]
Eligibility Criteria
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
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ECOG <= 2
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Patient eligible for intensive chemotherapy
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Who provide their written informed consent
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Liver workup: transaminases < 3x normal, bilirubin < 1.5 X normal
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Creatinine clearance > 60ml/mn
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LVEF >= 50%.
Exclusion Criteria:
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Patients with FLT3 ITD or TKD mutation
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Patients with tuberculosis
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Patients with documented active infection with COVID 19
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Patients with hereditary fructose intolerance (HFI)
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Uncontrolled infection
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Active or past infection with Hep B, C or HIV+
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Not Affiliated with French social security system or no beneficiary from such system
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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.
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Breastfeeding women
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Minors
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Adults under guardianship, curatorship or safeguard of justice
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Hypersensitivity to any of the active ingredients or excipients
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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.
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Nantes University Hospital
Investigators
- Principal Investigator: MATHILDE HUNAULT, University Hospital, Angers
- Principal Investigator: MARC BERNARD, CHU Rennes
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RC22_0372