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

  • STATUS
    Recruiting
  • End date
    Dec 1, 2027
  • participants needed
    50
  • sponsor
    Jeanette Lundin
Updated on 5 March 2021

Summary

Ibrutinib, an inhibitor of Brutons 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.

Details
Condition Chronic Lymphocytic Leukemia, Lymphocytic Leukemia, Chronic, Chronic Lymphocytic Leukemia, Lymphocytic Leukemia, Chronic, leukemia chronic lymphocytic, chronic lymphocytic leukemia (cll), small lymphocytic lymphoma, b-cell small lymphocytic lymphoma
Treatment Ibrutinib
Clinical Study IdentifierNCT04771507
SponsorJeanette Lundin
Last Modified on5 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Laboratory test results
Absolute neutrophil count >/= 0.5 x 109/L
Platelet count >/= 30 x 109/L
Serum creatinine < 177 mol/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

Exclusion Criteria

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
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
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