Clinical trial NCT02055924 (phase 1, status: terminated)
Conditions: b-cell lymphoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: ibrutinib and immunochemotherapies
SMILES: NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1
Reason stopped: 
    ansm decision due to veino occlusive disease (security alert)
  
Eligibility criteria:

        Inclusion Criteria:

          1. Patients with any type of relapsed or refractory B-cell lymphoma will be eligible in
             groups A, A bis, B and B bis (during the dose escalation and the expansion parts of
             the study) and untreated patients with mantle cell lymphoma will be eligible for group
             C (only during the expansion part of the study)

          2. Each patient (or their legally acceptable representative) must sign an informed
             consent form (ICF) indicating that he or she understands the purpose of and procedures
             required for the study and are willing to participate in the study

          3. Patients eligible for autologous stem cell transplantation (ASCT) for whom R-DHAP or
             R-DHAOx is an acceptable therapy regarding the investigator's opinion

          4. Measurable disease defined by at least one single node or tumor lesion > 1.5 cm

          5. Patients who received prior therapy with at least one but no more than two lines
             therapies for B-Cell Lymphoma (except for patients included in group C during the
             expansion part of the study)

          6. Aged between 18 years and 70 years (included)

          7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          8. Any of the following hematology values within 14 days prior to inclusion and prior to
             the first dose of study drug :

               1. Absolute neutrophil count (ANC) > 1,000 cells/mm3 (1.0 x 109/L) unless if bone
                  marrow infiltration from lymphoma

               2. Spontaneous Platelets count > 75,000 cells/mm3 (75 x 109/L) within 7 days of any
                  platelet transfusion (allowed up to 50 x 109/L if due to bone marrow infiltration
                  from lymphoma)

          9. Patients assessed as being able to receive full doses of R-DHA(P/Ox) for 3 cycles or 4
             cycles for patients included in group C of the expansion phase

         10. Life expectancy of ≥ 90 days (3 months)

         11. Women of childbearing potential* and men who are sexually active must be practicing a
             highly effective method of birth control during the study and during 12 months after
             the end of treatments. Men must agree to not donate sperm during the study and during
             12 months after the end of treatments

         12. Women of childbearing potential must have a negative serum beta human chorionic
             gonadotropin (β-hCG) or urine pregnancy test at Screening

        Exclusion Criteria:

          1. Previous treatment with a BTK inhibitor

          2. Patients who progressed or became refractory while on treatment with a
             phosphoinositide 3-kinase (PI3K) inhibitors

          3. Inability to tolerate 4 courses of high dose ara-C / platin compound, especially if
             due to underlying comorbidities

          4. History of stroke or intracranial hemorrhage within 6 months prior to the first dose
             of study drug

          5. Major surgery, within 4 weeks prior to the first dose of study drug

          6. Known bleeding diathesis

          7. Condition that requires therapeutic anticoagulation with Vitamin K antagonists

          8. Condition that requires treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5)
             inhibitor

          9. Any life-threatening illness, serious medical condition, laboratory abnormality, organ
             system dysfunction or psychiatric illness which, in the investigator's opinion, could
             compromise the patient's safety, interfere with the absorption or metabolism of
             ibrutinib capsules, or put the study outcomes at undue risk and that would prevent the
             patient from signing the informed consent form

         10. Known central nervous system or meningeal involvement by lymphoma

         11. Contraindication to any drug contained in these regimen

         12. Known history of human immunodeficiency virus (HIV)

         13. Known active Hepatitis C Virus (HCV; RNA polymerase chain reaction (PCR)-positive) or
             active Hepatitis B Virus infection (HBs Ag positive or DNA PCR-positive) or any
             uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
             Patients with PCR-negative for hepatitis B virus (HBV) are permitted in the study.

         14. Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiography or
             multiple uptake gated acquisition (MUGA) scan

         15. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior
             to the first dose of study drug, or any Class 3 (moderate) or Class 4 (severe) cardiac
             disease as defined by the New York Heart Association Functional Classification

         16. Any of the following biochemical values within 14 days prior to inclusion and prior to
             the first dose of study drug :

               1. Serum glutamic-oxaloacetic transaminase/aspartate aminotransferase (SGOT/ASAT) or
                  serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALAT) > 3.0 x
                  upper limit of normal (ULN)

               2. Serum total bilirubin > 2.0 mg/dL (34 µmol/L), except in patients with hemolytic
                  anemia or with Gilbert syndrome,

               3. Calculated creatinine clearance of < 50 mL /min (for patients who will have DHAOx
                  chemotherapy) or < 70 mL/min (for patients who will have DHAP chemotherapy)

         17. Patients with pre-existing ≥ Grade 2 neuropathy

         18. Prior history of malignancies other than lymphoma (except for basal cell or squamous
             cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the
             patient has been free of the disease for ≥ 3 years

         19. Use of any standard or experimental anti-cancer drug therapy within 28 days prior to
             the first dose of study drug

         20. Women who are pregnant or breastfeeding

         21. Medical history of hepatic chronic disease whatever the anteriority

         22. Sinusoidal obstruction syndrome (Veno-Occlusive Disease (VOD)) whatever the
             anteriority