A Pilot Study on Intermittent Ibrutinib in Patients With Advanced-phase Chronic Lymphocytic Leukemia (CLL) (IbruOnOff)

February 24, 2021 updated by: Jeanette Lundin

A Pilot Study on Intermittent and Repeated Dosing of Ibrutinib in the Treatment of Patients With Advanced-phase Chronic Lymphocytic Leukemia (CLL)

Ibrutinib, an inhibitor of Bruton´s tyrosine kinase (BTK) is approved in CLL as continuous, daily administration of 420 mg orally until progression. Ibrutinib drug costs in health care are rapidly increasing and are difficult to predict, as long-term follow up analyses have shown that many patients remain on therapy for several years, in some cases even many years. It has been observed that patients who stop ibrutinib due to side effects may often remain with continued CLL disease control i.e. in stable partial remission even when off ibrutinib therapy. There are also emerging data on mutations within BTK, with loss of efficacy of ibrutinib, during long-term continuous administration. These observations raise the question whether alternative dosing strategies may be feasible. This pilot study will explore intermittent and repeated dosing of ibrutinib, until alternative therapy is required due to resistance or intolerance to ibrutinib. An "ON-OFF" dosing strategy will be applied, where advanced-phase CLL patients who have received at least 6 months of ibrutinib and who have achieved a stable PR will stop ibrutinib and be followed off therapy until clinical progression, at which ibrutinib will be re-instituted. Such "ON-OFF" ibrutinib cycles may be repeated until non-tolerability or resistance, or need of continuous dosing of ibrutinib (i.e. early progression when off the drug). If successful, the study will indicate a way forward towards reducing ibrutinib drug costs in health care without affecting long-term disease control, possibly also with fewer ibrutinib-related side effects due to a lower cumulative dose of ibrutinib. Long-term effects on potential mutations within BTK and its downstream signaling molecules will also be analysed.

Study Overview

Status

Status

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

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 (Anticipated)

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.
50

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 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 Contact Backup

Study Locations

  • Norway
      • Trondheim, Norway, 7030
        • Recruiting
        • St Olavs hospital
        • Contact:
        • Principal Investigator:
          • Emadoldin Feyzi, MD PhD
  • Sweden
      • Gothenburg, Sweden, 413 45
        • Not yet recruiting
        • Sahlgrenska University Hospital
        • Contact:
        • Principal Investigator:
          • Catharina Lewerin, MD PhD
      • Stockholm, Sweden, 17176
        • Recruiting
        • Karolinska University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jeanette Lundin, MD PhD
      • Umeå, Sweden, 901 85
        • Not yet recruiting
        • Norrland's University Hospital
        • Contact:
        • Principal Investigator:
          • Floretin Späth, MD PhD
      • Uppsala, Sweden, 751 85
      • Örebro, Sweden, 701 85
    • Dalarna
      • Falun, Dalarna, Sweden, 791 82
    • Gävleborg
      • Gävle, Gävleborg, Sweden, 801 87
    • Skåne
      • Lund, Skåne, Sweden, 222 42
        • Not yet recruiting
        • Skåne University Hospital
        • Contact:
        • Principal Investigator:
          • Jenny Klintman, MD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Ability to understand and voluntarily provide written informed consent and comply with the requirements of the study.
  2. Age 18 years and older. There is no upper age limit in this trial.
  3. Able to adhere to the study visit schedule and other protocol requirements.
  4. Before start ibrutinib for the first time: diagnosed with CLL/SLL and active disease in need of treatment after having failed chemoimmunotherapy for CLL defined as a) refractory according to iwCLL criteria; or b) relapsed and deemed not suitable for additional chemo- or chemoimmunotherapy or c) del 17p and/or TP53 mutation irrespective of prior therapy.
  5. Having received at least 6 months of ibrutinib therapy and having achieved at least clinical PR according to IWCLL criteria.
  6. ECOG performance status of </= 2 at screening.

  7. Laboratory test results:

    • Absolute neutrophil count >/= 0.5 x 109/L
    • Platelet count >/= 30 x 109/L
    • Serum creatinine < 177 µmol/L
    • ASAT (SGOT) and ALAT (SGPT) >/= 2 x ULN or >/= 5 x ULN unless attributable to CLL/SLL
  8. Disease free of prior malignancies for >/= 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
  9. Agree to use reliable forms of contraception. Post-menopausal females and surgically sterilized females are exempt from this criterion.

Exclusion Criteria:

  1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  2. Pregnant or breast feeding females.
  3. Any condition, including the presence of laboratory abnormalities, which according to the responsible physician places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  4. Use of any other experimental therapy within the last 14 days.
  5. Concurrent use of other anti-cancer agents or treatments than ibrutinib (except a low dose of corticosteroids, max 10 mg of prednisone/day).
  6. Positivity for HIV or infectious hepatitis, type A, B or C.
  7. Opportunistic infections within the last 3 months.
  8. Patient planned for or being a potential candidate for allo-SCT.
  9. Uncontrolled hemolytic anemia or autoimmune thrombocytopenia.
  10. CNS involvement or history of Richter's transformation.
  11. Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon) within 28 days of the first dose of ibrutinib.
  12. Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor.

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: Intermittent ibrutinib
Intermittent treatment with ibrutinib.
Drug: Ibrutinib
Ibrutinib will be stopped at inclusion in the and the patient will be followed OFF therapy. At clinical progress, ibrutinib will be restarted (ON period) at the same standard dose as used at inclusion. When the patient achieve at least partial response again, a new OFF period is started, and so on.
Other Names:
  • Imbruvica

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
Safety measured as type, frequency and severity of adverse events.
Time Frame: Through study completion, 1-24 months.
Type, frequency and severity of adverse events and relationship to intermittent ibrutinib dosing.
Through study completion, 1-24 months.

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
Overall response at each treatment cycle.
Time Frame: Through study completion, 1-24 months.
Response when re-starting ibrutinib, at each cycle.
Through study completion, 1-24 months.
Time to PR and PR-L at each cycle.
Time Frame: Through study completion, 1-24 months.
Time to partial response (PR) and partial response with persistent lymphocytosis (PR-L) when re-starting ibrutinib, at each cycle.
Through study completion, 1-24 months.
Time to stop until restart of ibrutinib due to progress
Time Frame: Through study completion, 1-24 months.
Time from the patient going off ibrutinib until it has to be re-started due to progressive, for each cycle.disease (PD), at each cycle.
Through study completion, 1-24 months.
Number of ibrutinib treatment cycles and OFF therapy periods.
Time Frame: Through study completion, 1-24 months.
The number of cycles each patient stop and re-start ibrutinib.
Through study completion, 1-24 months.
Cumulative dose of ibrutinib.
Time Frame: Through study completion, 1-24 months.
The cumulative dose of ibrutinib for each patient.
Through study completion, 1-24 months.
Overall survival.
Time Frame: Through study completion, 1-24 months.
Overall survival.
Through study completion, 1-24 months.
Risk of early rebound phenomenon.
Time Frame: Through study completion, 1-24 months.
Observation of early rebound phenomemon at each re-start of ibrutinib.
Through study completion, 1-24 months.
Time to need of alternative treatment.
Time Frame: Through study completion, 1-24 months.
Time to need of alternative treatment.
Through study completion, 1-24 months.

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.
Jeanette Lundin

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: Jeanette Lundin, MD PhD, Karolinska University Hospital

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.
February 23, 2018

Primary Completion (Anticipated)

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.
April 1, 2023

Study Completion (Anticipated)

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 1, 2027

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).
February 19, 2021

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.
February 24, 2021

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.
February 25, 2021

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.
February 25, 2021

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.
February 24, 2021

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.
February 1, 2021

More Information

Terms related to this study

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.
  • HCK-LT-CLL02/2017

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.

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