Adult Patients With Adverse Risk Acute Myeloblastic Leukemia
Conditions
Brief summary
To search for a Maximum Tolerated Dose (MTD) for the combination of daratumumab and induction chemotherapy with Idarubicin and cytarabine or CPX-351 in patients with Acute Myeloblastic Leukemia (AML) of poor prognosis
Interventions
DRUGDarzalex
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)
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Continual Reassessment Method for MTD
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 2022 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 | — |
Countries
France
Contacts
CONTACTPIERRE PETERLIN
PRINCIPAL_INVESTIGATORMATHILDE HUNAULT
University Hospital, Angers
PRINCIPAL_INVESTIGATORMARC BERNARD
Rennes University Hospital
Outcome results
None listed