Combination Chemotherapy in Patients With Newly Diagnosed BPDCN (LpDessai)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
• Intervention / Treatment: Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eric DECONINCK, MD, PhD; Phone Number: +3381668166; Email: edeconinck@chu-besancon.fr

Study Locations

• France
  • Amiens, France, 80090
    • Clinique de l'Europe
  • Besancon, France, 25030
    • CHU Besançon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemotherapy

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/m²Patients <65y and albuminemia <35 g/l and/or CrCl (MDRD) <60 ml/min: 1000 mg/m² IVPatients ≥65y and albuminemia >35 g/l and CrCl (MDRD) > 60 ml/min : 1000 mg/m²Patients ≥ 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)

What is the study measuring?

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))

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal residual disease analysis	presence of PDC cell blast (CD56 +, NG2 +, BDCA2low, BDCA4low, CD123low, cTCL1high as measured by flow cytometry)	24 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Collaborators: Centre Hospitalier Universitaire Dijon; Centre Henri Becquerel; Maisonneuve-Rosemont Hospital; UMR1098, EFS BFC, BESANCON; Inserm CIC1431, CHU Besancon

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Actual): February 13, 2023
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LpDessai

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No