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Trial record 6 of 329 for:    IBRUTINIB

Ibrutinib + R-CHOP Followed by Ibrutinib Maintenance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03731234
Recruitment Status : Recruiting
First Posted : November 6, 2018
Last Update Posted : February 6, 2020
Sponsor:
Collaborator:
Janssen-Cilag S.p.A.
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

Brief Summary:

This is a prospective, multicenter, single arm, phase II trial in patients with ≥ 18 and <80 years with poor-prognosis (IPI ≥ 2) and newly diagnosed ABC-DLBCL.

Aim of the study is to assess the efficacy and the safety of R-CHOP in combination with ibrutinib for 6 cycles followed by ibrutinib maintenance for 18 months in ABC-DLBCL patients achieving at least a PR after the induction phase


Condition or disease Intervention/treatment Phase
DLBCL Drug: Ibrutinib Phase 2

Detailed Description:

Step 1 - Screening phase If central review will confirm and define the diagnosis of ABC-DLBCL according the COO, eligible patients will have to sign an additional informed consent prior to receive the study subsequent treatment.

Step 2 - study treatment phases Induction phase: 5 courses of R-CHOP every 21 days combined with ibrutinib (560 mg/day, continuously).

Maintenance phase: patients achieving a CR or a PR after 5 courses of RI-CHOP21 will enter the maintenance phase with ibrutinib (560 mg/day, continuously) for 18 months.

Radiotherapy could be delivered as consolidation treatment at the end of R-chemotherapy, according to Institution local clinical practice, in patients with focal PET positive residual disease and to bone extranodal lesions or scrotum, if testicular involvement irrespective of initial tumor diameter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Ibrutinib in combination to rituximab-CHOP followed by ibrutinib maintenance
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Multicenter Single Arm Study to Evaluate the Efficacy and Safety of Ibrutinib in Combination to Rituximab-CHOP Followed by Ibrutinib Maintenance in Untreated Patients With Activated-B-Cell (ABC)-DLBCL at Intermediate-high and High Risk (IPI ≥2)
Actual Study Start Date : July 2, 2019
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: Ibrutinib+R-CHOP
Screening phase for selection of Activated-B-Cell (ABC)-DLBCL Induction phase: R-CHOP21 x 5 cycles in combination with ibrutinib Maintenance phase: maintenance with Ibrutinib for 18 months for patients responding to the induction phase (CR or PR)
Drug: Ibrutinib
Ibrutinib in combination to rituximab-CHOP followed by ibrutinib maintenance
Other Name: IMBRUVICA (commercial name)




Primary Outcome Measures :
  1. Progression-free survival (PFS) (1st time point of assessment) [ Time Frame: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (24 months) ]
    PFS of the high/high-intermediate risk patients from date of enrolment

  2. Progression-free survival (PFS) (2nd time point of assessment) [ Time Frame: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (36 months) ]
    PFS of the high/high-intermediate risk patients from date of enrolment

  3. Progression-free survival (PFS) (3dr time point of assessment) [ Time Frame: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (48 months) ]
    PFS of the high/high-intermediate risk patients from date of enrolment


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Time between the date of enrolment and the date of death from any cause (24, 36 and 48 months). ]
    Overall Survival

  2. Complete response and Overall Response (CR+PR) rate at the end of induction [ Time Frame: End of induction (EOI) (4 months) ]
    Complete response and Overall Response

  3. Duration of response (DOR) [ Time Frame: From the date when criteria for response are met (CR or PR) until the date of progression or relapse. Patients without relapse or progression or death from other causes will be censored at their last assessment date (24 months from response date) ]
    Duration of response

  4. Complete remission (CRR) after ibrutinib maintenance [ Time Frame: End of treatment (EOT) (up to 24 months) ]
    Complete remission after ibrutinib maintenance

  5. Event Free Survival (EFS) [ Time Frame: From the date of enrolment to the date of disease progression, relapse from CR, initiation of subsequent systemic anti-lymphoma therapy after the least 6 cycles of RI-CHOP (each cycle is 21 days), or death whichever occurs first (24, 36 and 48 months) ]
    Event Free Survival



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  • Histologically confirmed DLBCL not otherwise specified (NOS)
  • ABC type defined by Lymph2Cx on the NanoString platform. Note: A formalin fixed paraffin embedded lymph node or tumor biopsy specimen must be submitted to Central Pathology for review during the Screening Period. The specimen must have been acquired by a surgical incision or excision biopsy or from a core needle biopsy
  • Previously untreated disease
  • Age ≥ 18 and < 65 years
  • IPI score ≥ 2
  • 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 × 10 9 /L independent of growth factor support, platelet count ≥ 100,000/mm 3 or ≥ 50,000/mm 3 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/1.73m 2 , 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 non-hepatic 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
  • No peripheral neuropathy or active neurological non-neoplastic disease of CNS
  • No major surgical intervention prior 3 months to enrolment if not due to lymphoma and/or no 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. - Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [Beta-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.
  • Life expectancy > 6 months

EXCLUSION CRITERIA

  • DLBCL including High grade B-cell Lymphomas, both with double hit and NOS according to the 2017 Revised WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues
  • GCB-DLBCL after centralized COO profiling
  • Any other histologies than DLBCL: composite or transformed disease, patients with follicular lymphoma IIIB and large B-cell lymphoma with IRF4 rearrangement.
  • Primary mediastinal lymphoma (PMBL)
  • Known central nervous system lymphoma
  • Primary testicular 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.
  • 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03731234


Contacts
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Contact: Maurizio Martelli, Prof 00390649974779 martelli@bce.uniroma1.it

Locations
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Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
Janssen-Cilag S.p.A.
Investigators
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Principal Investigator: Maurizio Martelli, Prof. Dipartimento di Medicina Traslazionale e di Precisione, Università 'La Sapienza'

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Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT03731234    
Other Study ID Numbers: FIL_RI-CHOP
First Posted: November 6, 2018    Key Record Dates
Last Update Posted: February 6, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fondazione Italiana Linfomi ONLUS:
DLBCL
Activated-B-Cell DLBCL
Ibrutinib
Phase II
Additional relevant MeSH terms:
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Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents