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

Sponsor

Fondazione Italiana Linfomi ONLUS (Other)

Overall Status

Terminated

CT.gov ID

NCT02670317

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B-Cell	Drug: Obinutuzumab Drug: Ibrutinib Drug: CHOP	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Sep 1, 2016

Actual Primary Completion Date :

Feb 1, 2017

Actual Study Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: G CHOP 21 + Ibrutinib Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib.	Drug: Obinutuzumab Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib. Other Names: GA101 Drug: Ibrutinib Patients will receive a maximum of 6 courses of G-CHOP-21 followed by 2 doses of Obinutuzumab in combination with Ibrutinib. Other Names: Imbruvica Drug: 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. Other Names: Cyclophosphamide, doxorubicin, vincristine, and prednisone Hydroxydaunomycin, Oncovin

Arm

Intervention/Treatment

Experimental: G CHOP 21 + Ibrutinib

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

Drug: Obinutuzumab

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

Other Names:

GA101

Drug: Ibrutinib

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

Other Names:

Imbruvica

Drug: 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.

Other Names:

Cyclophosphamide, doxorubicin, vincristine, and prednisone

Hydroxydaunomycin, Oncovin

Outcome Measures

Primary Outcome Measures

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

Overall Survival (OS) [2 years]
Complete Remission (CR) Rate [6 months]
Overall Response Rate (ORR) [6 months]
The Duration Of Response (DOR) after the end of treatment [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 [β-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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IRCCS Candiolo - Fondazione del Piemonte per l'oncologia	Candiolo	TO	Italy
2	AO SS. Antonio e Biagio e C. Arrigo	Alessandria		Italy	15121
3	AOU Policlinico Consorziale	Bari		Italy
4	AO Papa Giovanni XXIII	Bergamo		Italy
5	Ospedale di Bolzano	Bolzano		Italy
6	Ospedale Businco	Cagliari		Italy
7	AO di Cosenza	Cosenza		Italy
8	AOU Careggi	Firenze		Italy
9	P.O. Vito Fazzi	Lecce		Italy
10	IRST Meldola	Meldola		Italy
11	Ospedale Papardo	Messina		Italy
12	Istituto Europeo Oncologico	Milano		Italy
13	AOU Policlinico di Modena	Modena		Italy
14	Ospedale San Gerardo	Monza		Italy
15	IRCCS Napoli Pascale	Napoli		Italy
16	Ospedale Maggiore della Carità	Novara		Italy
17	AOOR Villa Sofia Cervello	Palermo		Italy
18	AOU di Parma	Parma		Italy
19	Ospedale G. Da Saliceto	Piacenza		Italy
20	AOR San Carlo	Potenza		Italy
21	Ospedale Degli Infermi	Rimini		Italy
22	Policlinico Gemelli	Roma		Italy
23	Policlinico Umberto I	Roma		Italy
24	Humanitas	Rozzano		Italy
25	Casa Sollievo della Sofferenza	San Giovanni Rotondo		Italy
26	AOU Città Della Salute e Della Scienza Ematologia Universitaria	Torino		Italy
27	AOU Città Della Salute e Della Scienza SC Ematologia	Torino		Italy
28	AOU di Udine	Udine		Italy
29	Ospedale di Circolo e Fondazione Macchi	Varese		Italy