Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma

NCT03458260 | Completed Phase 2 DMC

• 1 other identifier: PIVeR
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 22

Brief Summary

This study will evaluate the efficacy of Pixantrone with rituximab, ifosfamide and etoposide as measured by the overall metabolic response rate after 2 cycles of treatment or at permanent treatment discontinuation.

Conditions

Aggressive Non-Hodgkin Lymphoma

Keywords

Diffuse Large B-Cell Lymphoma (DLBCL); relapsed or refractory

Outcome Measures

Primary Outcomes (1)

• Overall Metabolic Response rate (OMR) according to local investigator

  by local investigator according to Lugano classification 2014

  After 42 days of treatment (2 cycles) or at permanent treatment discontinuation.

Secondary Outcomes (7)

• Complete Metabolic Response rate (CMR) according to local investigator

  After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.

• Overall Metabolic Response rate (OMR) according to central review

  After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.

• Complete Metabolic Response rate (CMR) according to central review

  After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.

• Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  After 42 or 126 days of treatment (2 or 6 cycles of 21 days) or at permanent treatment discontinuation.

• Number of patients for whom Partial Metabolic Response (PMR) is transformed into CMR

  After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.

Study Arms (1)

Experimental

EXPERIMENTAL

Pixantrone plus rituximab, ifosfamide and etoposide.

Drug: Pixantrone; Other: Ifosfamide; Other: Etoposide; Other: Rituximab; Procedure: Transplant

Interventions

Pixantrone DRUG

6 cycles - dose = 80mg/m²

Also known as: Pixuvri

Experimental

Ifosfamide OTHER

6 cycles - 1500 mg/m2

Also known as: Holoxan

Experimental

Etoposide OTHER

6 cycles - 150 mg/m2

Also known as: Vepeside

Experimental

Rituximab OTHER

6 cycles - 375 mg/m2

Also known as: Mabthera

Experimental

Transplant PROCEDURE

after 2 or 6 cycles

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven CD20+ aggressive non-Hodgkin lymphoma (diffuse large B-cell lymphoma (DLBCL), de novo or transformed DLBCL from previously untreated low grade non-Hodgkin lymphoma or grade 3b follicular lymphoma) as per the World Health Organization (WHO) 2016 criteria
• Relapsed or refractory disease, defined as follows:
• Patients eligible for ASCT who failed to achieve a Complete Response (CR) after at least one salvage therapy (eg, Rituximab-Etoposide- Methylprednisolone - Cytarabine - Cisplatin (R-ESHAP) or Rituximab- Dexamethasone- High-dose Cytarabine - Cisplatin (R-DHAP), patients who were previously refractory to Rituximab-Ifosfamide-Cytarabine-Etoposide (R-ICE) (stable disease or progressive disease) are not eligible to the study)
• Or patients in first relapse after Autologous Stem Cell Transplant (ASCT)
• Or patients not eligible for ASCT who failed to achieve a CR after at least one prior treatment (and no more than 4 previous lines) or in relapse after at least one prior treatment (and no more than 4 previous lines).
• Age \> or =18 years
• Eastern Cooperative Oncology Group (ECOG) performance status \< or = 2
• Subjects must have evaluable disease based on positron emission tomography (PET-CT) scan
• Minimum life expectancy of 6 months
• Signed written informed consent
• Patient covered by any social security system
• Men must agree to use a barrier method of contraception during the treatment period and until 6 months after the last dose of chemotherapy
• Women of childbearing potential must agree to use an adequate method of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception during the treatment period and until 12 months after the last dose of chemotherapy

You may not qualify if:

• Any other histological type of lymphoma (Burkitt lymphoma, mantle-cell lymphoma…)
• Any history of previously treated indolent non-Hodgkin lymphoma
• Symptomatic central nervous system or meningeal involvement by the lymphoma
• Contraindication to any drug contained in the Pixantrone with rituximab, ifosfamide and etoposide regimen
• Treatment with any investigational drug within 28 days before the first study drug administration
• Any of the following lab abnormalities unless related to the lymphoma or bone marrow infiltration:
• Absolute neutrophil count (ANC) \< 1.0 G/L
• Platelet count \< 100 G/L
• Creatinine clearance \< 40 mL/min for patients \< 70 y, or creatinine clearance \< 60 mL/min for patients \> or = 70 y, by Modification of Diet in Renal Disease (MDRD) method.
• Total bilirubin level \> 1,5 x Upper Limit of Normal (ULN)
• Serum ASpartate Transaminase (AST) or ALanine Transaminase (ALT)\> 2,5x ULN
• Known Human Immunodeficiency Virus (HIV) positive
• Active hepatitis C virus (HCV) (Positive HCV serology with positive Polymerase Chain Reaction (PCR) for HCV RNA)
• Active hepatitis B (HB) :
• HBsAg positive

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead

Study Sites (22)

AZ Sint Jan

Bruges, Belgium

Location

Institut Jules Bordet - Centre des tumeurs de l'ULB

Brussels, Belgium

Location

Centre Hospitalier de Jolimont

Haine-Saint-Paul, Belgium

Location

CH d'Avignon

Avignon, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, France

Location

CHU Jean Minjoz

Besançon, France

Location

Hôpital Haut-Lévèque

Bordeaux, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, France

Location

Clinique Victor Hugo

Le Mans, France

Location

CHRU de Lille

Lille, France

Location

CHU Lyon Sud

Lyon, France

Location

CHU de la Conception

Marseille, France

Location

Centre Lacassagne

Nice, France

Location

Hopital La Pitié Salpétriere

Paris, France

Location

Hôpital St louis

Paris, France

Location

CHU de Poitiers

Poitiers, France

Location

Centre Hospitalier Annecy Genevois

Pringy, France

Location

CH de Cornouaille

Quimper, France

Location

Hôpital Robert Debré

Reims, France

Location

CHU de Rouen

Rouen, France

Location

CHU de Strasbourg

Strasbourg, France

Location

CHU de Tours

Tours, France

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

pixantrone; Ifosfamide; Etoposide; Rituximab; Transplantation

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Surgical Procedures, Operative

Study Officials

• Luc-Matthieu Fornecker

  CHU de Strasbourg

  PRINCIPAL INVESTIGATOR

• Eric Van den Neste

  UCL St Luc Bruxelles

  PRINCIPAL INVESTIGATOR

• Sandy Amorin

  Hôpital St Louis - Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 8, 2018
• Study Start: December 26, 2018
• Primary Completion: December 24, 2024
• Study Completion: December 24, 2024
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (19); BE (3)