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

NCT ID: NCT04771507

Last Updated: 2021-02-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-23
• Study Completion Date: 2027-12-01

Brief 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 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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intermittent ibrutinib

Intermittent treatment with ibrutinib.

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Imbruvica

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jeanette Lundin

OTHER

Sponsor Role: lead

Responsible Party

Jeanette Lundin

Consultant, Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jeanette Lundin, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

St Olavs Hospital

Trondheim, , Norway

Site Status: RECRUITING

Falu lasarett

Falun, Dalarna County, Sweden

Site Status: RECRUITING

Gävle Hospital

Gävle, Gävleborg County, Sweden

Site Status: RECRUITING

Skåne University Hospital

Lund, Skåne County, Sweden

Site Status: NOT_YET_RECRUITING

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status: NOT_YET_RECRUITING

Örebro University Hospital

Örebro, , Sweden

Site Status: RECRUITING

Karolinska University Hospital

Stockholm, , Sweden

Site Status: RECRUITING

Norrland's University Hospital

Umeå, , Sweden

Site Status: NOT_YET_RECRUITING

Akademiska hospital

Uppsala, , Sweden

Site Status: RECRUITING

Countries

Norway; Sweden

Central Contacts

Jeanette Lundin, MD PhD

Role: CONTACT

jeanette.lundin@sll.se

0700 85 67 86 ext. 46

Sanna Nyström, PhD

Role: CONTACT

sanna.nystrom@sll.se

08 517 759 27 ext. 46

Facility Contacts

Emadoldin Feyzi, MD PhD

Role: primary

emadoldin.feyzi@stolav.no

Max Flogegård

Role: primary

max.flogegard@ltdalarna.se

Anders Uddevik, MD

Role: primary

anders.uddevik@regiongavleborg.se

Jenny Klintman, MD

Role: primary

jenny.klintman@skane.se

Catharina Lewerin, MD PhD

Role: primary

catharina.lewerin@vgregion.se

Magdalena Kättström, MD

Role: primary

magdalena.kattstrom@regionorebrolan.se

Jeanette Lundin, MD PhD

Role: primary

jeanette.lundin@sll.se

Sanna Nyström, PhD

Role: backup

sanna.nystrom@sll.se

Florentin Späth, MD PhD

Role: primary

florentin.spaeth@umu.se

Mattias Mattsson, MD

Role: primary

mattias.mattsson@akademiska.se

Other Identifiers

HCK-LT-CLL02/2017

Identifier Type: -

Identifier Source: org_study_id