Combination Chemotherapy in Patients With Newly Diagnosed BPDCN

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Clinical Trial

— LpDessai  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03599960
• Other study ID #: LpDessai
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 2, 2019
• Est. completion date: November 2024

Study information

• Verified date: February 2024
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 26
• Est. completion date: November 2024
• Est. primary completion date: February 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
• Neoplasms

Intervention

Drug:
• Chemotherapy
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)

Locations

Country	Name	City	State
France	Clinique de L'Europe	Amiens
France	Chu Besancon	Besancon

Sponsors (6)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon	Centre Henri Becquerel, Centre Hospitalier Universitaire Dijon, Inserm CIC1431, CHU Besancon, Maisonneuve-Rosemont Hospital, UMR1098, EFS BFC, BESANCON

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minimal residual disease analysis	presence of PDC cell blast (CD56 +, NG2 +, BDCA2low, BDCA4low, CD123low, cTCL1high as measured by flow cytometry)	24 months
Primary	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	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))
Secondary	Overall survival	Overall survival	24 months
Secondary	Relapse-free survival	Relapse-free survival	24 months
Secondary	Residual L-asparaginase activity	Residual L-asparaginase activity	12 weeks (Day 8 of each chemotherapy cycle (each cycle is 21 days))
Secondary	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))