Clinical trial NCT03458260: Study of Pixantrone in CD20+ Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Aggressive Non-Hodgkin Lymphoma
Keywords: Diffuse Large B-Cell Lymphoma (DLBCL)
relapsed or refractory
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
First posted: 2018-03-08
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Metabolic Response rate (OMR) according to local investigator
timeFrame: After 42 days of treatment (2 cycles) or at permanent treatment discontinuation.
Secondary outcomes:
measure: Complete Metabolic Response rate (CMR) according to local investigator
timeFrame: After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
measure: Overall Metabolic Response rate (OMR) according to central review
timeFrame: After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
measure: Complete Metabolic Response rate (CMR) according to central review
timeFrame: After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
measure: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: After 42 or 126 days of treatment (2 or 6 cycles of 21 days) or at permanent treatment discontinuation.
measure: Number of patients for whom Partial Metabolic Response (PMR) is transformed into CMR
timeFrame: After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
measure: Rate of ASCT
timeFrame: After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
measure: Success of stem cell collection after treatment
timeFrame: After 42 days of treatment (2 cycles of 21 days) or at permanent treatment discontinuation.
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: AZ Sint Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet - Centre des tumeurs de l'ULB
city: Haine-Saint-Paul
country: Belgium
facility: Centre Hospitalier de Jolimont
city: Avignon
country: France
facility: CH d'Avignon
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Besançon
country: France
facility: CHU Jean Minjoz
city: Bordeaux
country: France
facility: Hôpital Haut-Lévèque
city: Chalon-sur-Saône
country: France
facility: Centre Hospitalier William Morey
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: CHU Lyon Sud
city: Marseille
country: France
facility: CHU de la Conception
city: Nice
country: France
facility: Centre Lacassagne
city: Paris
country: France
facility: Hopital La Pitié Salpétriere
city: Paris
country: France
facility: Hôpital St louis
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pringy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Quimper
country: France
facility: CH de Cornouaille
city: Reims
country: France
facility: Hôpital Robert Debré
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: CHU de Strasbourg
name: Luc-Matthieu Fornecker
role: PRINCIPAL_INVESTIGATOR
affiliation: UCL St Luc Bruxelles
name: Eric Van den Neste
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital St Louis - Paris
name: Sandy Amorin
role: PRINCIPAL_INVESTIGATOR
References: