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

NCT02670317 | Terminated Phase 2

• 2 other identifiers: FIL-GALILEO2015-005273-20
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 29

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.

Conditions

Lymphoma, B-Cell

Keywords

DLBCL; large B cell lymphoma; NHL

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (1)

G CHOP 21 + Ibrutinib

EXPERIMENTAL

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

Drug: Obinutuzumab; Drug: Ibrutinib; Drug: CHOP

Interventions

Obinutuzumab DRUG

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

Also known as: GA101

G CHOP 21 + Ibrutinib

Ibrutinib DRUG

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

Also known as: Imbruvica

G CHOP 21 + Ibrutinib

CHOP DRUG

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.

Also known as: Cyclophosphamide, doxorubicin, vincristine, and prednisone, Hydroxydaunomycin, Oncovin

G CHOP 21 + Ibrutinib

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (29)

IRCCS Candiolo - Fondazione del Piemonte per l'oncologia

Candiolo, TO, Italy

Location

AO SS. Antonio e Biagio e C. Arrigo

Alessandria, 15121, Italy

Location

AOU Policlinico Consorziale

Bari, Italy

Location

AO Papa Giovanni XXIII

Bergamo, Italy

Location

Ospedale di Bolzano

Bolzano, Italy

Location

Ospedale Businco

Cagliari, Italy

Location

AO di Cosenza

Cosenza, Italy

Location

AOU Careggi

Florence, Italy

Location

P.O. Vito Fazzi

Lecce, Italy

Location

IRST Meldola

Meldola, Italy

Location

Ospedale Papardo

Messina, Italy

Location

Istituto Europeo Oncologico

Milan, Italy

Location

AOU Policlinico di Modena

Modena, Italy

Location

Ospedale San Gerardo

Monza, Italy

Location

IRCCS Napoli Pascale

Napoli, Italy

Location

Ospedale Maggiore della Carità

Novara, Italy

Location

AOOR Villa Sofia Cervello

Palermo, Italy

Location

AOU di Parma

Parma, Italy

Location

Ospedale G. Da Saliceto

Piacenza, Italy

Location

AOR San Carlo

Potenza, Italy

Location

Ospedale Degli Infermi

Rimini, Italy

Location

Policlinico Gemelli

Roma, Italy

Location

Policlinico Umberto I

Roma, Italy

Location

Humanitas

Rozzano, Italy

Location

Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

AOU Città Della Salute e Della Scienza Ematologia Universitaria

Torino, Italy

Location

AOU Città Della Salute e Della Scienza SC Ematologia

Torino, Italy

Location

AOU di Udine

Udine, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, Italy

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

obinutuzumab; ibrutinib; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Maurizio Martelli, MD

  Policlinico Umberto I - Università "La Sapienza"

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: February 1, 2016
• Study Start: September 1, 2016
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: March 20, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (29)