Ibrutinib, Bortezomib and Rituximab-CHOP for the Treatment of Elderly Patients With CD20+ DLBCL, IPI ≥ 2 (ImbruVeRCHOP)

December 10, 2024 updated by: Prof. Dr. Clemens Schmitt

Ibrutinib (Imbruvica®), Bortezomib (Velcade®) s.c., Rituximab, CHOP for the Treatment of Elderly Patients (Age 61-80 Years) With CD20+ Diffuse Large B-cell Lymphoma, IPI ≥ 2

The ImbruVeRCHOP-Trials is an Investigator-initiated, single-arm, multi-center, prospective, open phase I/II trial to evaluate the efficacy and feasibility of Ibrutinib and Bortezomib in the therapy of higher-risk DLBCL patients of different molecular subtypes and to correlate outcome with clinical, molecular and imaging-guided response parameters. The protocol includes a safety run-in phase, i.e. the phase I part of the study, to uncover unexpected toxicities that may arise in the context of Ibrutinib and Bortezomib co-administered with the R-CHOP backbone. The safety run-in phase is followed by the phase II part of the trial. About 34 patients will be included. Additional 8-11 German university centers and 1-5 in Austria will participate in this trial. The study treatment includes a pre-phase therapy with Prednisone and 6 cycles of a combined immuno-chemotherapy with the anti-CD20 antibody Rituximab together with 6 cycles of a chemotherapy consisting of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone plus Bortezomib and Ibrutinib followed by two additional 3-week cycles of Rituximab. Secondary endpoints are the predictive power of subtypes (such as GCB/ABC-"cell-of-origin"), markers of minimal residual disease over time and during-the-study-determined markers (e.g. gene signatures) to identify patients who benefit from this treatment addition.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Cycle 1 (C1): At C1/day d2, there will be a CT- or ultrasound-guided re-biopsy of a lymphoma lesion that is accessible for biopsy without considerable risk for the patient.

Cycle 2 (C2): After C2, a post-Interim CT will be performed (eventually FDG and FLT PET-CT imaging added to the protocol by amendment).

Cycle 3 (C3): At C3/d0 (prior to therapy), there will also be another bone marrow aspirate for MRD follow-up. At C3/d2, there will be a re-biopsy of a lymphoma site in case of a residual lesion by CT that is accessible for biopsy without considerable risk for the patient. Biopsies can be obtained CT- or ultrasound-guided.

End of treatment/post-therapy: The end-of-treatment visit is required for all subjects, irrespective of a completion of all 8 cycles of therapy or exit of the study protocol. It has to be scheduled approximately 4 to 6 weeks after the last cycle. A total of 7 Follow up visits is planned over 30 months of follow up.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
38

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 13353
        • Charité - Universitätsmedizin Berlin, Hematology, Oncology and Tumor Immunology, Campus Virchow Klinikum

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

57 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Written informed consent indicating that they understand the purpose of and procedures required for the study, including biomarkers and are willing to participate in the study
  • Age ≥ 61 years and ≤ 80 years
  • CD20-positive diffuse large B-cell lymphoma (DLBCL); including T-cell-rich large B-cell lymphoma, anaplastic large B-cell lymphoma, plasmablastic lymphoma; follicular lymphoma grade 3b or primary transformed follicular lymphoma at initial diagnosis or highgrade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements or high-grade B-cell lymphoma NOS
  • Lymphoma biopsy native, fresh-frozen for genome-wide transcriptome array or RNA-Seq analyses (gene expression profiling [GEP]) for molecular subtype diagnosis
  • Willingness to consent to a re-biopsy in C1/day d2, and - in case of a residual lesion by interim CT - in C3/d2 if it can be obtained without inadequate risk
  • Unfavorable risk profile according to the IPI score (IPI ≥ 2)
  • Performance status (ECOG) 0-2
  • Bi-dimensionally measurable disease (measurable by CT scan or MRI)
  • Cardiac ejection fraction ≥ 50 % without clinically significant abnormalities
  • Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count ≥ 1,00/μL independent of growth factor support and platelet count ≥ 100,000/μL or ≥ 50,000/μL if bone marrow involvement independent of transfusion support in either situation
  • Adequate renal function as documented by serum creatinine level < 2 x ULN or estimated GFR ≥ 40 ml/min/1,73m²
  • Adequate hepatic function (total bilirubin ≤ 1,5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, alanine aminotransferase ALT and aspartate aminotransferase AST ≤ 3 x ULN)
  • Life expectancy > 6 months
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [ß-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study.
  • 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 1 month after the last dose of study drug. For males, these restrictions apply for 3 month after the last dose of study drug.

Exclusion Criteria:

  • Unable to sign informed consent
  • Secondary transformed B-NHL or types of NHL other than DLBCL and its subtypes according to WHO classification
  • Prior therapy for DLBCL
  • Known central nervous system lymphoma
  • CNS involvement by lymphoma or any evidence of spinal cord compression. Brain CT/MRI is only mandatory (within 4 weeks prior to study entrance) in case of clinical suspicion of CNS involvement by lymphoma
  • Major surgery within 4 weeks of study entrance
  • History of stroke or intracranial hemorrhage within 6 months prior to study entrance
  • Anticoagulation with Warfarin or equivalent vitamin K antagonists (e.g, Phenprocoumon)
  • 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 or 4 cardiac disease as defined by NYHA
  • treatment with strong CYP3A inhibitors
  • Known history of human immunodeficiency virus HIV or active Hepatitis C virus or active Hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous iv antibiotics
  • Vaccination with live, attenuated vaccines within 3 weeks of study entrance
  • History of solid organ transplantation
  • Pregnant or nursing females
  • Prior malignancy (except adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical cancer in situ, or any other cancer for which the patient has been in remission for at least 5 years)
  • Known hypersensitivity or contraindication to any of the study drugs, its ingredients or recombinant human antibodies and contrast agents
  • Pre-existing polyneuropathy of any kind > grade I
  • Severe chronic obstructive pulmonary disease with hypoxemia
  • Current or recent (within the last 30 days prior to enrollment) treatment with another investigational drug or participation in another clinical trial
  • Evidence of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or patient at high risk from treatment complications
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigators opinion, could compromise the subjects safety, interfere with the absorption or metabolism of ibrutinib capsules or put the study outcomes at undue risk
  • Any co-existing medical or psychological condition that would compromise the ability to give informed consent
  • Subjects who are legally detained in an official institution
  • Subjects who may be dependent on the sponsor, the investigator or the trial sites, have to be exclude from the trial
  • Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ibrutinib and Bortezomib + R-CHOP
A pre-phase therapy with Prednisone 100 mg p.o. is mandatory from d-4 until d0. Patients receive 6 cycles of a combined immunochemotherapy with the anti-CD20 antibody Rituximab (375 mg/m2 d0 or d1) together with 6 cycles of a chemotherapy consisting of Cyclophosphamide (750 mg/m2 d1), Doxorubicin (50 mg/m2 d1), Vincristine 1 mg absolute d1), Prednisone (100 mg absolute p.o. d1-5) and Bortezomib s.c. (1.3 mg/m2 C1 on d3 and 8, other cycles d1 and d8), in 21-day intervals and Ibrutinib 560 mg p.o. for individuals < 65 years and 420 mg p.o. for individuals ≥ 65 years (from d6 of C1 until d21 of C6), followed by two additional 3-week cycles of Rituximab (375 mg/m2).
Drug: Ibrutinib and Bortezomib + R-CHOP
A pre-phase therapy with Prednisone 100 mg p.o. is mandatory from d-4 until d0. Patients receive 6 cycles of a combined immunochemotherapy with the anti-CD20 antibody Rituximab (375 mg/m2 d0 or d1) together with 6 cycles of a chemotherapy consisting of Cyclophosphamide (750 mg/m2 d1), Doxorubicin (50 mg/m2 d1), Vincristine 1 mg absolute d1), Prednisone (100 mg absolute p.o. d1-5) and Bortezomib s.c. (1.3 mg/m2 C1 on d3 and 8, other cycles d1 and d8), in 21-day intervals and Ibrutinib 560 mg p.o. for individuals < 65 years and 420 mg p.o. for individuals ≥ 65 years (from d6 of C1 until d21 of C6), followed by two additional 3-week cycles of Rituximab (375 mg/m2).
Other Names:
  • Ibrutinib (Imbruvica®), Bortezomib (Velcade®)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
2-year progression-free survival
Time Frame: 2 years after completion of treatment
progression-free survival after 2 years after end of treatment
2 years after completion of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: through study completion, an average of 3 years
through study completion, an average of 3 years
1y- and 2y-PFS for patients based on cell-of-origin (COO, i.e. GCB vs. ABC subtype)
Time Frame: 1 and 2 years after end of treatment
1 and 2 years after end of treatment
number of patients with complete remission in all patients and based on cell-of-origin
Time Frame: 2 years after end of treatment
2 years after end of treatment
Predictive power of markers for Minimal Residual Disease (MRD) over time
Time Frame: 2 years after end of treatment
2 years after end of treatment
Objective Response Rate (ORR) in all patients and based on cell-of-origin
Time Frame: 2 years after end of treatment
Proportion of patients with reduction in tumor burden in all patients and based on cell-of-origin
2 years after end of treatment
Disease-Free Survival in all patients and based on cell-of-origin
Time Frame: 2 years after end of treatment
number of patients with disease-free survival in all patients and based on cell-of-origin
2 years after end of treatment
Overall survival in all patients and based on cell-of-origin
Time Frame: 2 years after end of treatment
2 years after end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Prof. Dr. Clemens Schmitt

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Charite University, Berlin, Germany
Janssen-Cilag Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Clemens Schmitt, Prof. Dr., Representative of the Sponsor, National Coordinator, Principal Investigator

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 17, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 12, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 12, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EudraCT-Nr.: 2015-003429-32

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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