Biomarker Driven Intensified ChemoImmunotherapy With Early CNS Prophylaxis (Bio-CHIC)

June 20, 2024 updated by: Nordic Lymphoma Group

Biomarker Driven and Dose Intensified Chemoimmunotherapy With Early CNS Prophylaxis in Patients Less Than 65 Years With High Risk Diffuse Large B-Cell Lymphoma

This study is testing whether stratification of the patients according to biological risk factors for different treatment groups will improve the outcome of patients with clinically high diffuse large B-cell lymphoma (DLBCL).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

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

For young clinically high-risk diffuse large B-cell lymphoma (DLBCL) patients the optimal therapy has not been established. Previous Nordic phase II studies, where dose-dense chemoimmunotherapy (R-CHOEP-14) with systemic CNS prophylaxis (HD-Mtx and HD-AraC) was given, demonstrated favorable outcome in comparison to historical controls. However, the patients with biological risk factors, such as translocation of bcl2 and myc oncogenes or and/or high BCL2 and MYC expression or deletion 17p and/or high P53 expression had significantly higher risk of death, as compared to patients without aberrations. The figures provide evidence for an unmet clinical need for the patients with biological risk factors, and underscore the importance of a clinical trial, where both biological and clinical risk factors play a role in the treatment planning.

In this trial treatment intensity varies according to presence or absence of biological risk factors. All patients receive a prephase medication consisting of prednisone and vincristine and two cycles of R-CHOP and high dose (HD) methotrexate. Subsequently, depending on the biological risk factors either four additional cycles of R-CHOEP (standard arm with no risk factors) or four dose adjusted R-EPOCH courses (experimental arm with risk factors) are given, followed by one course of high dose cytarabine (Ara-C) and R. R-CHOEP courses should be given with a two-week and R-EPOCH with a three-week interval.

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 (Estimated)

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.
120

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

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Denmark
      • Aarhus, Denmark
        • Aarhus University Hospital
      • Copenhagen, Denmark, 2100
        • Dept of Haematology, Rigshospitalet
      • Herlev, Denmark
        • Dept of Haematology, Herlev Hospital, Copenhagen
      • Odense, Denmark, 5000
        • Dept haematology, Odense University hospital
      • Roskilde, Denmark, 4000
        • Dept of Haematology, Sjaellands University hospital, Roskilde
  • Finland
      • Helsinki, Finland, 00029
        • Helsinki University Hospital Cancer Centre
      • Jyväskylä, Finland, 40620
        • Keski-Suomen Keskussairaala
      • Kuopio, Finland, 70029
        • Kuopio University Hospital
      • Tampere, Finland, 33521
        • TAYS
      • Turku, Finland, 20520
        • Turku University Hospital, Syöpäklinikka
  • Norway
      • Bergen, Norway, 5021
        • Dept. of Oncology, Helse Bergen HF Haukeland sykehus
      • Oslo, Norway
        • Oslo University Hospital
      • Stavanger, Norway, 4011
        • Dept. of Haematology and Oncology, Helse Stavander HF sykehuset
      • Tromsø, Norway, 9038
        • Dept. of Oncology, Universitetssykehuset i Nord-Norge HF
      • Trondheim, Norway, 7006
        • Dept of Oncology, St. Olavs hospital HF
  • Sweden
      • Lund, Sweden
        • Skåne University Hospital

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

14 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 - 64 years

  • Histologically confirmed CD20+ DLBCL based on revised WHO 2008 Lymphoma Classification. The following subgroups and variants can be included:

    • ALK-positive large B-cell lymphoma
    • Intravascular large B-cell lymphoma
    • T-cell rich B-cell lymphoma
    • Myc/BCL-2 double hit lymphoma
    • Follicular lymphomas grade 3b
    • DLBCL with previously undiagnosed concurrent small cell infiltration in bone marrow, lymph node, or extranodal site and lymphomas intermediate between DLBCL and Burkitt's lymphoma are allowed
    • Posttransplantation lymphoma (PTLD), discordant or transformed lymphoma are NOT allowed

  • Patients in at least stage II with age adjusted IPI score of 2 or 3:

    • Stage III /IV and elevated LDH
    • Stage III/IV and WHO performance status 2 - 3
    • Stage II and elevated LDH and WHO performance status 2 - 3

  • And/or patients with site specific risk factors for CNS recurrence defined as follows

    • More than one extranodal site
    • Testicular lymphoma, stage IIE and higher
    • Paranasal sinus and orbital lymphoma with destruction of bone
    • Large cell lymphoma infiltration of the bone marrow
  • Previously untreated, except steroids allowed
  • WHO performance status 0-3
  • Written informed consent

Exclusion Criteria:

  • Severe cardiac disease: cardiac function grade 3-4, left ventricular ejection fraction <45%
  • Impaired bone marrow liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule (Hemoglobin < 9 g/dL, ANC < 1.5 × 109/L, Platelet count < 75 × 109/L, creatinine clearance < 40 mL/min, ALT/AST > 2.5 x ULN, bilirubin 1.5 x ULN, INR > 1.5)
  • Pregnancy/lactation
  • Men and women of reproductive potential not agreeing to use effective contraception during treatment and for 18 months after completion of treatment (Effective contraception is combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), hormone-releasing IUD, bilateral tubal occlusion, vasectomised partner, or sexual abstinence
  • Patients with other severe medical problems, including active infections, cardiac or pulmonary disease, history of PML and with an expected short survival for non-lymphoma reasons
  • Known HIV positivity
  • Active or chronic hepatitis B virus (HBV) infection (defined as positive HBsAg serology), or active hepatitis C virus (HCV) infection (defined by antibody serology testing). HBsAg, HBcAb, and HCVAb must be tested during screening. Patients who have protective titers of HBsAb along negative HBsAg after vaccination or prior but cured hepatitis B are eligible.
  • Vaccination with a live vaccine within one month prior to randomization
  • Patients with a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for ≥ 5 years prior to enrollment
  • Earlier treatment containing anthracyclines
  • Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
  • CNS disease as diagnosed by MRI or CSF cytology. Positive CSF flow cytometry below diagnostic threshold level by cytology is allowed
  • Transformed lymphoma
  • Primary mediastinal B-cell lymphoma
  • Pleural or peritoneal fluid that cannot be drained safely
  • Hypersensitivity to the active substance or any of the other ingredients
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
  • Patients participating in other clinical studies, unless followed for survival
  • Lower urinary tract constriction, which cannot be treated adequately
  • Degenerative and toxic encephalopathy
  • Neuromuscular disease

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: Non-Randomized
  • Interventional Model: Parallel 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: Group A
Biologically low risk group, R-CHOEP-14
Combination product: R-CHOEP
rituximab, cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone
Experimental: Group B
Biologically high risk group, DA-EPOCH-R
Combination product: DA-EPOCH-R
dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab

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
Time to treatment failure (TTF) of the patients with biological risk factors
Time Frame: At 3 years
Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.
At 3 years

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
Time to treatment failure (TTF) at 3 years from date of registration of all patients and the patients in the low risk group
Time Frame: At 3 years
Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.
At 3 years
Incidence of treatment-emergent adverse events (Safety and tolerability)
Time Frame: During the treatment period at the end of each cycle (14 or 21 days) up to 6 months. In addition, severe late toxicities during follow-up at 6 months intervals through study completion, an average of 5.5 years.
Number of patients with treatment-related adverse events graded according to the NCI CTCAE v 4.03
During the treatment period at the end of each cycle (14 or 21 days) up to 6 months. In addition, severe late toxicities during follow-up at 6 months intervals through study completion, an average of 5.5 years.
Clinical response rate of all patients and the patients with biological risk factors
Time Frame: At the end of treatment cycles 2 and 7. Each cycle is two (group A) or three weeks (group B)
Number of patients with complete or partial response
At the end of treatment cycles 2 and 7. Each cycle is two (group A) or three weeks (group B)
CNS relapse rate
Time Frame: At 1,5 years
Number of patients with CNS progression
At 1,5 years
Progression free survival rate (PFS) of all patients and the patients with biological risk factors
Time Frame: At 3 years
At 3 years
Overall survival rate (OS) of all patients and the patients with biological risk factors
Time Frame: At 3 years
At 3 years
Molecular correlates for survival
Time Frame: At 3 years
Identification of genomic aberrations (for example mutations and translocations), gene expression profiles and protein expression from the tumor tissue and circulation that predict clinical course of the disease
At 3 years

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.
Nordic Lymphoma Group

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.
Helsinki University Central Hospital
Aarhus University Hospital

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: Sirpa Leppa, prof, Helsinki University Hospital Cancer Centre

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.
August 4, 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.
January 31, 2021

Study Completion (Estimated)

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.
December 31, 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).
September 5, 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.
September 21, 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.
September 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.
June 21, 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.
June 20, 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.
June 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.
  • NLG-LBC-06

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

individual deidentified participant data (including data dictionaries) will be shared

IPD Sharing Time Frame

Beginning 3 months and ending 5 years following article publication

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Clinical Trials on Lymphoma, Large B-Cell, Diffuse

Clinical Trials on R-CHOEP

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings