Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Conditions
Brief summary
Patients with suspected BPDCN and meeting eligibility criteria will be enrolled in the study. First, BPDCN diagnosis will be confirmed by anatomic pathology (Dr Petrella T, Montreal) and cytologic plus immunophenotyping analysis (Pr Garnache Ottou F, UMR1098 BESANCON). Patients will then receive three 21 days cycles of a combination of chemotherapy (Ida/Metho/L-asp/Dex), followed by an evaluation. Patients with complete response (CR) or complete response with incomplete bone marrow recovery (CRi) will undergo an allo- or auto-SCT and those who are not eligible to the transplantation will have successive 28 days cycles of chemotherapy (Metho/L-asp/Dex). Patients who did not respond to the treatment will be treated by physicians. All patients will be followed for 24 months.
Interventions
DRUGChemotherapy
* Idarubicin 12mg/m2 IV at D1 * Methotrexate at D1 (24H infusion, alkaline hydration, leucovorin rescue): * Patients \<65y and albuminemia \>35 g/l and CrCl (MDRD)\>60 ml/min: 3000 mg/m² * Patients \<65y and albuminemia \<35 g/l and/or CrCl (MDRD) \<60 ml/min: 1000 mg/m² IV * Patients ≥65y and albuminemia \>35 g/l and CrCl (MDRD) \> 60 ml/min : 1000 mg/m² * Patients ≥ 65y and albuminemia \< 35 g/l and/or CrCl (MDRD) \< 60 ml/min : 500 mg/m² * L-asparaginase (SPECTRILA) : 5000 units/m² IV at D2, 5, 8, 11 (switch to Erwinia asparaginase/Cirsantaspase 25 000 U/m² with the same drug regimen in case of hypersensitivity reactions or significant diminution of asparaginase activity) * Dexamethasone 40mg PO or IV at D1-4 (dose diminution at 20 mg for Age ≥65y)
Sponsors
UMR1098, EFS BFC, BESANCON
Centre Henri Becquerel
Maisonneuve-Rosemont Hospital
Centre Hospitalier Universitaire Dijon
Inserm CIC1431, CHU Besancon
Centre Hospitalier Universitaire de Besancon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients will receive 3 cycles of a combination of chemotherapy (Met/Ida/L-Asp/Dex)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed BPDCN established by a blood or bone marrow immunophenotypic diagnosis by flow cytometric and/or by the anatomic pathology study of a skin biopsy using validated diagnostic criteria (Swerdlow SH CE et al., World Health Organisation Classification of Tumors, 2008; Garnache-Ottou et al., 2009; Angelot et al., 2012; Julia et al., 2014) or patients with confirmed isolated skin lesion. * 18 years of age or older * No prior cytotoxic therapy except \<2 week of corticosteroids or hydroxyurea * ECOG ≤2 * Written informed consent * Affiliation to the French social security scheme
Exclusion criteria
* Cardiac contra-indication to anthracyclines: cardiac dysfunction events (NYHA grade 3 or 4 and/or LVEF\<50%) * Hepatocellular abnormalities except if considered related to the BPDCN: 1. ASAT (SGOT) and/or ALAT (SGPT) \> 5 x ULN 2. Total bilirubin ≥ 2.5 x ULN * Creatinine level \>1.5x ULN or creatinine clearance (MDRD)\<50 mL/mn * Prior thrombotic event * Active hepatitis B or C virus infection * HIV positive * Serious medical or psychiatric illness that could interfere with the completion of treatment * Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. * Pregnant and lactating female patients * Patients diagnosed with or treated for another malignancy within 2 years before study enrollment or with residual disease (basal cell carcinoma or cervical carcinoma in situ patients may be enrolled if they have undergone complete resection)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with complete response after 3 cycles of chemotherapy | 12 weeks (3 weeks after 3 cycles of chemotherapy (each cycle is 21 days)) | Proportion of patients with complete response after 3 cycles of chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with response (complete or partial) after 3 cycles of chemotherapy | 12 weeks (3 weeks after 3 cycles of chemotherapy (each cycle is 21 days)) | Proportion of patients with response (complete or partial) after 3 cycles of chemotherapy |
| Overall survival | 24 months | Overall survival |
| Residual L-asparaginase activity | 12 weeks (Day 8 of each chemotherapy cycle (each cycle is 21 days)) | Residual L-asparaginase activity |
| Anti-L-asparaginase antibodies levels | 12 weeks (Day 8 of each chemotherapy cycle (each cycle is 21 days)) | Evaluation of the titer of the anti-asparaginase antibody |
| Relapse-free survival | 24 months | Relapse-free survival |
Other
| Measure | Time frame | Description |
|---|---|---|
| Minimal residual disease analysis | 24 months | presence of PDC cell blast (CD56 +, NG2 +, BDCA2low, BDCA4low, CD123low, cTCL1high as measured by flow cytometry) |
Countries
France
Outcome results
None listed