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

A Multicentre, Phase II, Open Label, Single Arm Study of Pixantrone in Patients With CD20-positive Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma Treated With Rituximab, Ifosfamide and Etoposide.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aggressive Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Pixantrone; Other: Ifosfamide; Other: Etoposide; Other: Rituximab; Procedure: Transplant

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Thomas PLEAU-PISON; Phone Number: 33472663861; Email: thomas.pleau-pison@lysarc.org

Study Locations

• Belgium
  • Brugge, Belgium
    • AZ Sint Jan
  • Brussels, Belgium
    • Institut Jules Bordet - Centre des tumeurs de l'ULB
  • Haine-Saint-Paul, Belgium
    • Centre Hospitalier de Jolimont
• France
  • Avignon, France
    • CH d'Avignon
  • Bayonne, France
    • Centre Hospitalier de la Côte Basque
  • Besançon, France
    • CHU Jean Minjoz
  • Bordeaux, France
    • Hôpital Haut-Lévêque
  • Chalon-sur-Saône, France
    • Centre Hospitalier William Morey
  • Le Mans, France
    • Clinique Victor Hugo
  • Lille, France
    • CHRU de Lille
  • Lyon, France
    • CHU Lyon Sud
  • Marseille, France
    • CHU de La CONCEPTION
  • Nice, France
    • Centre Lacassagne
  • Paris, France
    • Hopital St Louis
  • Paris, France
    • Hôpital La Pitié Salpêtrière
  • Poitiers, France
    • Chu de Poitiers
  • Pringy, France
    • Centre Hospitalier Annecy Genevois
  • Quimper, France
    • CH de Cornouaille
  • Reims, France
    • Hopital Robert Debre
  • Rouen, France
    • CHU de Rouen
  • Strasbourg, France
    • CHU de Strasbourg
  • Tours, France
    • CHU de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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

2. Relapsed or refractory disease, defined as follows:

   1. 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)
   2. Or patients in first relapse after Autologous Stem Cell Transplant (ASCT)
   3. 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).
3. Age > or =18 years
4. Eastern Cooperative Oncology Group (ECOG) performance status < or = 2
5. Subjects must have evaluable disease based on positron emission tomography (PET-CT) scan
6. Minimum life expectancy of 6 months
7. Signed written informed consent
8. Patient covered by any social security system
9. Men must agree to use a barrier method of contraception during the treatment period and until 6 months after the last dose of chemotherapy
10. 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

Exclusion Criteria:

1. Any other histological type of lymphoma (Burkitt lymphoma, mantle-cell lymphoma…)
2. Any history of previously treated indolent non-Hodgkin lymphoma
3. Symptomatic central nervous system or meningeal involvement by the lymphoma
4. Contraindication to any drug contained in the Pixantrone with rituximab, ifosfamide and etoposide regimen
5. Treatment with any investigational drug within 28 days before the first study drug administration

6. Any of the following lab abnormalities unless related to the lymphoma or bone marrow infiltration:

   1. Absolute neutrophil count (ANC) < 1.0 G/L
   2. Platelet count < 100 G/L
   3. 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.
   4. Total bilirubin level > 1,5 x Upper Limit of Normal (ULN)
   5. Serum ASpartate Transaminase (AST) or ALanine Transaminase (ALT)> 2,5x ULN
7. Known Human Immunodeficiency Virus (HIV) positive
8. Active hepatitis C virus (HCV) (Positive HCV serology with positive Polymerase Chain Reaction (PCR) for HCV RNA)

9. Active hepatitis B (HB) :

   1. HBsAg positive
   2. HBsAg negative, Ac anti-HBs positive and/or Ac anti-HB core (HBc) positive (Patients who are seropositive due to a history of hepatitis B vaccine are eligible. Patients with Ac anti-HBs positive and/or Ac anti-HBc positive and no history of hepatitis B vaccine are eligible only if PCR for HB virus DNA is negative)
10. Cumulative dose of doxorubicine or equivalent > 450mg/m2
11. Left ventricular ejection fraction (LVEF) < 50% measured by echocardiography or isotopic method
12. Congestive heart failure (any stage from New York Heart Association (NYHA) classification)
13. Uncontrolled arterial hypertension
14. Severe rhythmic heart disease
15. Uncontrolled ischemic heart disease, including patients with stable angina
16. Significant valvular heart disease
17. History of a myocardial infarction within 6 months prior to enrolment
18. Pregnant or lactating females
19. Prior history of malignancies with the exception of non-melanoma skin tumors (basal cell or squamous cell carcinoma) or in situ cervical carcinoma
20. Any serious active disease or co-morbid medical condition according to the investigator's decision
21. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
22. Use of any standard or experimental anti-cancer drug therapy within 28 days before the first study drug administration
23. Use of corticosteroids prior to baseline PET-CT
24. Person deprived of his/her liberty by a judicial or administrative decision
25. Person hospitalized without consent
26. Adult person under legal protection

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: Experimental; Pixantrone plus rituximab, ifosfamide and etoposide.	Drug: Pixantrone; 6 cycles - dose = 80mg/m²; Other Names: Pixuvri; Other: Ifosfamide; 6 cycles - 1500 mg/m2; Other Names: Holoxan; Other: Etoposide; 6 cycles - 150 mg/m2; Other Names: Vepeside; Other: Rituximab; 6 cycles - 375 mg/m2; Other Names: Mabthera; Procedure: Transplant; after 2 or 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Metabolic Response rate (CMR) according to local investigator	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	according to local investigator	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Complete Metabolic Response rate (CMR) according to central review	according to local investigator	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.
Rate of ASCT	Number of patients who perform an ASCT out of total number of patients	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Success of stem cell collection after treatment	Rate of successful stem cell collection	After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Investigators: Principal Investigator: Luc-Matthieu Fornecker, CHU de Strasbourg; Principal Investigator: Eric Van den Neste, UCL St Luc Bruxelles; Principal Investigator: Sandy Amorin, Hôpital St Louis - Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Actual): June 15, 2019
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: March 1, 2018
• First Posted (Actual): March 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: relapsed or refractory; Diffuse Large B-Cell Lymphoma (DLBCL)
• Additional Relevant MeSH Terms: Behavioral Symptoms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Aggression; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Etoposide; Ifosfamide; Rituximab; Pixantrone
• Other Study ID Numbers: PIVeR

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