Phase II Study About Combination CHOP-21, Obinutuzumab and Ibrutinib in Untreated Young High Risk DLBCL Patients.

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02670317
• Date of registration: 25/01/2016
• Prospective Registration: Yes
• Primary sponsor: Fondazione Italiana Linfomi ONLUS
• Public title: Phase II Study About Combination CHOP-21, Obinutuzumab and Ibrutinib in Untreated Young High Risk DLBCL Patients. FIL-GALILEO
• Scientific title: Multicenter Phase II Single Arm Open-label Study on the Feasibility, Safety and Efficacy of Combination of CHOP-21 Supplemented With Obinutuzumab and Ibrutinib in Untreated Young High Risk Diffuse Large B-cell Lymphoma (DLBCL) Patients.
• Date of first enrolment: September 2016
• Target sample size: 1
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02670317
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Italy

Contacts

• Name: Maurizio Martelli, MD
• Affiliation: Policlinico Umberto I - Università "La Sapienza"

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified
(NOS)

- Previously untreated disease

- Age 18-60

- Age adjusted IPI=2-3

- Ann Arbor stage II-IV disease

- Measurable disease = 1.5 cm in longest diameter, and measurable in 2 perpendicular
dimensions

- Normal blood count as defined as: absolute neutrophil count =1.0 × 109/L independent
of growth factor support, platelet count = 100,000/mm3 or =50,000/mm3 if bone marrow
(BM) involvement independent of transfusion support in either situation

- Normal organ functions defined as: creatinine =2 times the upper limit of normal (ULN)
or estimated Glomerular Filtration Rate (Cockroft- Gault) =40 ml/min/1.73m2, aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) =3× the ULN; total bilirubin
= 1.5 × the ULN unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic
origin: patients with documented Gilbert disease may be enrolled if total bilirubin is
= 3.0 × the ULN; International normalized ratio (INR) < 1.5 × the ULN in the absence
of therapeutic anticoagulation; partial thromboplastin time (PTT) or activated partial
thromboplastin time (aPTT) < 1.5 × the ULN in the absence of a lupus anticoagulant"

- Patients with occult or prior hepatitis B infection (defined as HBsAg negative,
anti-HBs positive and /or anti-HBc positive) may be included if hepatitis B virus
(HBV) DNA is undetectable. These patients must be willing to undergo bi-monthly DNA
testing and they should receive prophylaxis with Lamivudine

- No active hepatitis C virus (HCV) infection

- Known availability of biopsy material

- No Central Nervous System (CNS) disease (meningeal and/or brain involvement by
lymphoma)

- Absence of active infections

- Non peripheral neuropathy or active neurological non neoplastic disease of CNS

- Non major surgical intervention prior 3 months to enrolment if not due to lymphoma
and/or not other disease life-threatening that can compromise chemotherapy treatment

- Patient with a history of curatively treated basal or squamous cell carcinoma or
melanoma of the skin or in situ carcinoma of the cervix at any time prior to the
study.

- Patients with any other malignancy that has been treated with surgery alone with
curative intent and the malignancy has been in remission without treatment for at
least 5 years prior to enrolment.

- Women of childbearing potential and men who are sexually active must be practicing a
highly effective method of birth control during and after the study consistent with
local regulations regarding the use of birth control methods for subjects
participating in clinical trials. Men must agree to not donate sperm during and after
the study. For females, these restrictions apply for 6 months after the last dose of
study drug. For males, these restrictions apply for 6 months after the last dose of
study drug.

- Women of childbearing potential must have a negative serum (betahuman chorionic
gonadotropin [ß-hCG]) or urine pregnancy test at Screening. Women who are pregnant or
breastfeeding are ineligible for this study.

- Life expectancy > 6 months

- Sign (or their legally-acceptable representatives must sign) an informed consent
document indicating that they understand the purpose of and procedures required for
the study and are willing to participate in the study.

Exclusion Criteria:

- Any Other histologies than Diffuse Large B- Cell Lymphoma (DLBCL): composite or
transformed disease and patients with follicular lymphoma IIIB

- Primary mediastinal lymphoma (PMBL)

- Known central nervous system lymphoma

- Any prior lymphoma therapy

- Contraindication to any drug in the chemotherapy regimen

- Left ventricular ejection fraction (LVEF) < 50%

- Neuropathy = grade 2

- Seropositive for or active viral infection with HBV

- HBsAg positive

- HBsAg negative, anti-HBs positive and /or anti-HBc positive with detectable viral DNA

- Known seropositive active HCV

- Human immunodeficiency virus (HIV) infection

- Any of the following abnormal laboratory values (unless any of these abnormalities are
due to underlying lymphoma): creatinine = 2 times the ULN (unless creatinine clearance
normal, or calculated creatinine clearance < 40 mL/min (using the Cockcroft-Gault
formula); AST or ALT =3 × the ULN; total bilirubin >1.5 × the ULN: patients with
documented Gilbert disease may be enrolled if total bilirubin is = 3.0 × the ULN; INR
> 1.5 × the ULN in the absence of therapeutic anticoagulation; PTT or aPTT > 1.5 × the
ULN in the absence of a lupus anticoagulant"

- History of stroke or intracranial hemorrhage within the past 6 months.

- Requires anticoagulation with warfarin or equivalent vitamin K antagonists

- Requires treatment with strong CYP3A inhibitors

- History of clinically relevant liver or renal insufficiency; significant cardiac,
vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic,
hematologic, psychiatric, or metabolic disturbances

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

- Vaccinated with live, attenuated vaccines within 4 weeks of enrollment

- Presence of major neurological disorders

- any uncontrolled active systemic infection requiring intravenous (IV) antibiotics

- Major surgical intervention prior 4 weeks to enrollment if not due to lymphoma and/or
other disease life-threatening that can compromise chemotherapy treatment

- Prior malignancies other than lymphoma in the last 5 years with exception of currently
treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma
of the cervix

- Any other coexisting medical or psychological condition that would preclude
participation in the study or compromise ability to give informed consent.

- Any life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of ibrutinib capsules, or put the study outcomes at


Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Lymphoma, B-Cell

Intervention(s)

Drug: Obinutuzumab

Drug: CHOP

Drug: Ibrutinib

Primary Outcome(s)

The safety of G-CHOP-21 in combination with Ibrutinib in terms of proportion of patients experiencing grade 3 or greater extra-hematologic toxicity or treatment interruption for safety reasons or any toxic death during the 6 cycles of treatment [Time Frame: 5 months of treatment]

The efficacy of G-CHOP-21 in combination with Ibrutinib in terms of 2-yrs PFS (progression-free survival) [Time Frame: 2 years]

Secondary Outcome(s)

Overall Response Rate (ORR) [Time Frame: 6 months]

Overall Survival (OS) [Time Frame: 2 years]

The Duration Of Response (DOR) after the end of treatment [Time Frame: 2 years]

Complete Remission (CR) Rate [Time Frame: 6 months]

Secondary ID(s)

2015-005273-20

FIL-GALILEO

Source(s) of Monetary Support

Please refer to primary and secondary sponsors