Chronic Lymphocytic LeukemiaPhase 1/2IbruOnOffNCT04771507
A Pilot Study on Intermittent Ibrutinib in Patients With Advanced-phase Chronic Lymphocytic Leukemia (CLL)
A Phase 1/2 study testing Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Jeanette Lundin at 9 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 23 Feb 2018to 1 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and voluntarily provide written informed consent and comply with the requirements of the study.
- Age 18 years and older. There is no upper age limit in this trial.
- Able to adhere to the study visit schedule and other protocol requirements.
- 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.
- Having received at least 6 months of ibrutinib therapy and having achieved at least clinical PR according to IWCLL criteria.
- ECOG performance status of </= 2 at screening.
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- 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
- 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.
- Agree to use reliable forms of contraception. Post-menopausal females and surgically sterilized females are exempt from this criterion.
Who cannot join
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females.
- 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.
- Use of any other experimental therapy within the last 14 days.
- Concurrent use of other anti-cancer agents or treatments than ibrutinib (except a low dose of corticosteroids, max 10 mg of prednisone/day).
- Positivity for HIV or infectious hepatitis, type A, B or C.
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- Opportunistic infections within the last 3 months.
- Patient planned for or being a potential candidate for allo-SCT.
- Uncontrolled hemolytic anemia or autoimmune thrombocytopenia.
- CNS involvement or history of Richter's transformation.
- Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon) within 28 days of the first dose of ibrutinib.
- Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor.
Trial locations and contacts
9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 2 countries
Sweden8 sites, 8 recruiting
- Recruiting
Falu lasarett
Falun, Dalarna County, 791 82
Max Flogegård, max.flogegard@ltdalarna.se
Max Flogegård, MD
- Recruiting
Gävle Hospital
Gävle, Gävleborg County, 801 87
Anders Uddevik, MD, anders.uddevik@regiongavleborg.se
Anders Uddevik, MD
- Not yet recruiting
Sahlgrenska University Hospital
Gothenburg, 413 45
Catharina Lewerin, MD PhD, catharina.lewerin@vgregion.se
Catharina Lewerin, MD PhD
- Not yet recruiting
Skåne University Hospital
Lund, Skåne County, 222 42
Jenny Klintman, MD, jenny.klintman@skane.se
Jenny Klintman, MD
- Recruiting
Örebro University Hospital
Örebro, 701 85
Magdalena Kättström, MD, magdalena.kattstrom@regionorebrolan.se
Magdalena Kättström, MD
- Recruiting
Karolinska University Hospital
Stockholm, 17176
Jeanette Lundin, MD PhD, jeanette.lundin@sll.se
Sanna Nyström, PhD, sanna.nystrom@sll.se
- Not yet recruiting
Norrland's University Hospital
Umeå, 901 85
Florentin Späth, MD PhD, florentin.spaeth@umu.se
Floretin Späth, MD PhD
- Recruiting
Akademiska hospital
Uppsala, 751 85
Mattias Mattsson, MD, mattias.mattsson@akademiska.se
Mattias Mattsson, MD
Norway1 site, 1 recruiting
- Recruiting
St Olavs Hospital
Trondheim, 7030
Emadoldin Feyzi, MD PhD, emadoldin.feyzi@stolav.no
Emadoldin Feyzi, MD PhD
About this study
Official title: 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.
- Being tested
- Ibrutinib
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
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.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent ibrutinib | Experimental | Intermittent treatment with ibrutinib. Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety measured as type, frequency and severity of adverse events.
Type, frequency and severity of adverse events and relationship to intermittent ibrutinib dosing.
Measured: Through study completion, 1-24 months.
Secondary outcomes (8)
Overall response at each treatment cycle.
Response when re-starting ibrutinib, at each cycle.
Measured: Through study completion, 1-24 months.
Time to PR and PR-L at each cycle.
Time to partial response (PR) and partial response with persistent lymphocytosis (PR-L) when re-starting ibrutinib, at each cycle.
Measured: Through study completion, 1-24 months.
Time to stop until restart of ibrutinib due to progress
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.
Measured: Through study completion, 1-24 months.
Number of ibrutinib treatment cycles and OFF therapy periods.
The number of cycles each patient stop and re-start ibrutinib.
Measured: Through study completion, 1-24 months.
Cumulative dose of ibrutinib.
The cumulative dose of ibrutinib for each patient.
Measured: Through study completion, 1-24 months.
Overall survival.
Overall survival.
Measured: Through study completion, 1-24 months.
Risk of early rebound phenomenon.
Observation of early rebound phenomemon at each re-start of ibrutinib.
Measured: Through study completion, 1-24 months.
Time to need of alternative treatment.
Time to need of alternative treatment.
Measured: Through study completion, 1-24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start23 Feb 2018
- Primary completion1 Apr 2023 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients treated with ibrutinib for at least 6 months and have achieved at least partial response will after inclusion stop the ibrutinib treatment and be followed-up for the study. If progress, they will re-initiate ibrutinib treatment. When they achieve at least partial response they stop the treatment again, and so on.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jeanette Lundin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jeanette Lundin, Karolinska University Hospital
- Investigators
- Jeanette Lundin, MD PhD, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04771507
- Sponsor's protocol ID
- HCK-LT-CLL02/2017
- Acronym
- IbruOnOff
- Status last verified
- Feb 2021
- First submitted
- 19 Feb 2021
- Last updated
- 25 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study on Intermittent and Repeated Dosing of Ibrutinib in the Treatment of Patients With Advanced-phase Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT04771507
- Acronym / sponsor ID
- IbruOnOff / HCK-LT-CLL02/2017
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Jeanette LundinUniversity, hospital or other
- Study start
- 23 Feb 2018 (actual)
- Primary completion
- 1 Apr 2023 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 25 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients treated with ibrutinib for at least 6 months and have achieved at least partial response will after inclusion stop the ibrutinib treatment and be followed-up for the study. If progress, they will re-initiate ibrutinib treatment. When they achieve at least partial response they stop the treatment again, and so on.
| Arm | Type | Receives |
|---|---|---|
| Intermittent ibrutinib | Experimental | Drug: IbrutinibIntermittent treatment with ibrutinib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Ability to understand and voluntarily provide written informed consent and comply with the requirements of the study.
- Age 18 years and older. There is no upper age limit in this trial.
- Able to adhere to the study visit schedule and other protocol requirements.
- 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.
- Having received at least 6 months of ibrutinib therapy and having achieved at least clinical PR according to IWCLL criteria.
Key exclusion criteria (12 listed)
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females.
- 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.
- Use of any other experimental therapy within the last 14 days.
- Concurrent use of other anti-cancer agents or treatments than ibrutinib (except a low dose of corticosteroids, max 10 mg of prednisone/day).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: ImbruvicaIbrutinib 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. | Drug | Intermittent ibrutinib |
Primary outcome
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.
8 secondary outcomes
Overall response at each treatment cycle.
Time frame: 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 stop until restart of ibrutinib due to progress
Time frame: Through study completion, 1-24 months.
Number of ibrutinib treatment cycles and OFF therapy periods.
Time frame: Through study completion, 1-24 months.
Cumulative dose of ibrutinib.
Time frame: Through study completion, 1-24 months.
Overall survival.
Time frame: Through study completion, 1-24 months.
Risk of early rebound phenomenon.
Time frame: Through study completion, 1-24 months.
Time to need of alternative treatment.
Time frame: Through study completion, 1-24 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jeanette Lundin, MD PhD principal investigator
Karolinska University Hospital
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Jeanette Lundin at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Sweden, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jeanette Lundin, MD PhD (0700 85 67 86 ext. 46, jeanette.lundin@sll.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety measured as type, frequency and severity of adverse events. (time frame: Through study completion, 1-24 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2021.