Combination Chemotherapy in Patients With Newly Diagnosed BPDCN

Study Overview
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Brief Summary
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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.

Official Title
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Combination Chemotherapy (Methotrexate, L-asparaginase, Idarubicin and Dexamethasone) in Patients With Newly Diagnosed Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Conditions
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Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Intervention / Treatment
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* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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: ASAT (SGOT) and/or ALAT (SGPT) > 5 x ULN 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients will receive 3 cycles of a combination of chemotherapy (Met/Ida/L-Asp/Dex)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy<br> | Drug: Chemotherapy<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with complete response after 3 cycles of chemotherapy | 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)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with response (complete or partial) after 3 cycles of chemotherapy | 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)) | 
| Overall survival | Overall survival | 24 months | 
| Relapse-free survival | Relapse-free survival | 24 months | 
| Residual L-asparaginase activity | Residual L-asparaginase activity | 12 weeks (Day 8 of each chemotherapy cycle (each cycle is 21 days)) | 
| Anti-L-asparaginase antibodies levels | Evaluation of the titer of the anti-asparaginase antibody | 12 weeks (Day 8 of each chemotherapy cycle (each cycle is 21 days)) |