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

Sponsor
The Lymphoma Academic Research Organisation (Other)
Overall Status
Recruiting
CT.gov ID
NCT03458260
Collaborator
(none)
89
Enrollment
22
Locations
1
Arm
83.2
Anticipated Duration (Months)
4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Pixantrone
  • Other: Ifosfamide
  • Other: Etoposide
  • Other: Rituximab
  • Procedure: Transplant
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
89 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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.
Actual Study Start Date :
Mar 26, 2018
Actual Primary Completion Date :
Jun 15, 2019
Anticipated Study Completion Date :
Mar 1, 2025

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Overall Metabolic Response rate (OMR) according to local investigator [After 42 days of treatment (2 cycles) or at permanent treatment discontinuation.]

      by local investigator according to Lugano classification 2014

    Secondary Outcome Measures

    1. Complete Metabolic Response rate (CMR) according to local investigator [After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.]

      according to local investigator

    2. Overall Metabolic Response rate (OMR) according to central review [After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.]

      according to local investigator

    3. Complete Metabolic Response rate (CMR) according to central review [After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.]

      according to local investigator

    4. 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.]

    5. 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.]

    6. Rate of ASCT [After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.]

      Number of patients who perform an ASCT out of total number of patients

    7. Success of stem cell collection after treatment [After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.]

      Rate of successful stem cell collection

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    3. 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)

    4. Or patients in first relapse after Autologous Stem Cell Transplant (ASCT)

    5. 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).

    6. Age > or =18 years

    7. Eastern Cooperative Oncology Group (ECOG) performance status < or = 2

    8. Subjects must have evaluable disease based on positron emission tomography (PET-CT) scan

    9. Minimum life expectancy of 6 months

    10. Signed written informed consent

    11. Patient covered by any social security system

    12. Men must agree to use a barrier method of contraception during the treatment period and until 6 months after the last dose of chemotherapy

    13. 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:

    7. Absolute neutrophil count (ANC) < 1.0 G/L

    8. Platelet count < 100 G/L

    9. 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.

    10. Total bilirubin level > 1,5 x Upper Limit of Normal (ULN)

    11. Serum ASpartate Transaminase (AST) or ALanine Transaminase (ALT)> 2,5x ULN

    12. Known Human Immunodeficiency Virus (HIV) positive

    13. Active hepatitis C virus (HCV) (Positive HCV serology with positive Polymerase Chain Reaction (PCR) for HCV RNA)

    14. Active hepatitis B (HB) :

    15. HBsAg positive

    16. 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)

    17. Cumulative dose of doxorubicine or equivalent > 450mg/m2

    18. Left ventricular ejection fraction (LVEF) < 50% measured by echocardiography or isotopic method

    19. Congestive heart failure (any stage from New York Heart Association (NYHA) classification)

    20. Uncontrolled arterial hypertension

    21. Severe rhythmic heart disease

    22. Uncontrolled ischemic heart disease, including patients with stable angina

    23. Significant valvular heart disease

    24. History of a myocardial infarction within 6 months prior to enrolment

    25. Pregnant or lactating females

    26. Prior history of malignancies with the exception of non-melanoma skin tumors (basal cell or squamous cell carcinoma) or in situ cervical carcinoma

    27. Any serious active disease or co-morbid medical condition according to the investigator's decision

    28. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness

    29. Use of any standard or experimental anti-cancer drug therapy within 28 days before the first study drug administration

    30. Use of corticosteroids prior to baseline PET-CT

    31. Person deprived of his/her liberty by a judicial or administrative decision

    32. Person hospitalized without consent

    33. Adult person under legal protection

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 AZ Sint Jan Brugge Belgium
    2 Institut Jules Bordet - Centre des tumeurs de l'ULB Brussels Belgium
    3 Centre Hospitalier de Jolimont Haine-Saint-Paul Belgium
    4 CH d'Avignon Avignon France
    5 Centre Hospitalier de la Côte Basque Bayonne France
    6 CHU Jean Minjoz Besançon France
    7 Hôpital Haut-Lévèque Bordeaux France
    8 Centre Hospitalier William Morey Chalon-sur-Saône France
    9 Clinique Victor Hugo Le Mans France
    10 CHRU de Lille Lille France
    11 CHU Lyon Sud Lyon France
    12 CHU de la Conception Marseille France
    13 Centre Lacassagne Nice France
    14 Hopital La Pitié Salpétriere Paris France
    15 Hôpital St louis Paris France
    16 CHU de Poitiers Poitiers France
    17 Centre Hospitalier Annecy Genevois Pringy France
    18 CH de Cornouaille Quimper France
    19 Hôpital Robert Debré Reims France
    20 CHU de Rouen Rouen France
    21 CHU de Strasbourg Strasbourg France
    22 CHU de Tours Tours France

    Sponsors and Collaborators

    • 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    The Lymphoma Academic Research Organisation
    ClinicalTrials.gov Identifier:
    NCT03458260
    Other Study ID Numbers:
    • PIVeR
    First Posted:
    Mar 8, 2018
    Last Update Posted:
    May 6, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by The Lymphoma Academic Research Organisation
    Diffuse Large B-Cell Lymphoma (DLBCL)
    relapsed or refractory
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Non-Hodgkin
    Aggression
    Rituximab
    Etoposide
    Ifosfamide
    Pixantrone

    Study Results

    No Results Posted as of May 6, 2021