Aggressive Non-Hodgkin Lymphoma
Conditions
Keywords
Diffuse Large B-Cell Lymphoma (DLBCL), relapsed or refractory
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.
Detailed description
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.
Interventions
DRUGPixantrone
6 cycles - dose = 80mg/m²
OTHERIfosfamide
6 cycles - 1500 mg/m2
OTHEREtoposide
6 cycles - 150 mg/m2
OTHERRituximab
6 cycles - 375 mg/m2
PROCEDURETransplant
after 2 or 6 cycles
Sponsors
The Lymphoma Academic Research Organisation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| 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. | Number of patients for whom Partial Metabolic Response is transformed into CMR |
| 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 |
| 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 |
Countries
Belgium, France
Contacts
PRINCIPAL_INVESTIGATORLuc-Matthieu Fornecker
CHU de Strasbourg
PRINCIPAL_INVESTIGATOREric Van den Neste
UCL St Luc Bruxelles
PRINCIPAL_INVESTIGATORSandy Amorin
Hôpital St Louis - Paris
Outcome results
None listed