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

Lymphoma, B-Cell Clinical Trial

— FIL-GALILEO  

Official 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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02670317
• Other study ID #: FIL-GALILEO
• Secondary ID: 2015-005273-20
• Status: Terminated
• Phase: Phase 2
• First received: January 25, 2016
• Last updated: March 16, 2017
• Start date: September 2016
• Est. completion date: February 2017

Study information

• Verified date: March 2017
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, multicenter, single arm, phase II trial in young patients (18-60 years) with poor-prognosis (aaIPI 2 or 3) newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL).

Aim of the study is to assess the efficacy and the safety of G-CHOP in combination with ibrutinib.

Description:

This is a prospective, multicenter, single arm, phase II trial in young patients (18-60 years) with poor-prognosis (age-adjusted International Prognostic Index, aaIPI, 2 or 3) newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL).

Patient will receive 6 courses of G-CHOP21 (Obimutizumab- cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone) followed by 2 doses of Obinutuzumab supplemented with Ibrutinib. Duration of treatment will be 5 months plus 4-5 weeks for response evaluation.

During the study, disease status will be evaluated after the 4th cycle by computed tomography (CT) scan, and after end of treatment by imaging test (18FDG-PET [positron emission tomography] and CT scan).

Patients will be recruited over 2 years and followed for a minimum of 2 years after the end of the treatment phase.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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 undue risk.

• If female, the patient is pregnant or breast-feeding

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• Obinutuzumab
Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib.
• Ibrutinib
Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib.
• CHOP
Patients will receive a maximum of 6 courses of CHOP-21 in combination with Obinutuzumab (G) followed by 2 doses of Obinutuzumab in combination with Ibrutinib.

Locations

Country	Name	City	State
Italy	AO SS. Antonio e Biagio e C. Arrigo	Alessandria
Italy	AOU Policlinico Consorziale	Bari
Italy	AO Papa Giovanni XXIII	Bergamo
Italy	Ospedale di Bolzano	Bolzano
Italy	Ospedale Businco	Cagliari
Italy	IRCCS Candiolo - Fondazione del Piemonte per l'oncologia	Candiolo	TO
Italy	AO di Cosenza	Cosenza
Italy	AOU Careggi	Firenze
Italy	P.O. Vito Fazzi	Lecce
Italy	IRST Meldola	Meldola
Italy	Ospedale Papardo	Messina
Italy	Istituto Europeo Oncologico	Milano
Italy	AOU Policlinico di Modena	Modena
Italy	Ospedale San Gerardo	Monza
Italy	IRCCS Napoli Pascale	Napoli
Italy	Ospedale Maggiore della Carità	Novara
Italy	AOOR Villa Sofia Cervello	Palermo
Italy	AOU di Parma	Parma
Italy	Ospedale G. Da Saliceto	Piacenza
Italy	AOR San Carlo	Potenza
Italy	Ospedale Degli Infermi	Rimini
Italy	Policlinico Gemelli	Roma
Italy	Policlinico Umberto I	Roma
Italy	Humanitas	Rozzano
Italy	Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	AOU Città Della Salute e Della Scienza Ematologia Universitaria	Torino
Italy	AOU Città Della Salute e Della Scienza SC Ematologia	Torino
Italy	AOU di Udine	Udine
Italy	Ospedale di Circolo e Fondazione Macchi	Varese

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The efficacy of G-CHOP-21 in combination with Ibrutinib in terms of 2-yrs PFS (progression-free survival)		2 years
Primary	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		5 months of treatment
Secondary	Overall Survival (OS)		2 years
Secondary	Complete Remission (CR) Rate		6 months
Secondary	Overall Response Rate (ORR)		6 months
Secondary	The Duration Of Response (DOR) after the end of treatment		2 years