NCT04771507: IbruOnOff

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

Recruiting now Phase 1, PHASE2 Last updated 25 February 2021

What this trial tests

Phase 1, PHASE2 trial testing Ibrutinib in Chronic Lymphocytic Leukemia in 50 participants. Currently enrolling.

Timeline

23 February 2018

Primary endpoint
1 April 2023

1 December 2027

Quick facts

Lead sponsor	Jeanette Lundin
Phase	Phase 1, PHASE2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	50
Start date	23 February 2018
Primary completion	1 April 2023
Estimated completion	1 December 2027
Sites	9 locations across Sweden, Norway

Drugs / interventions tested

• Ibrutinib (ibrutinib) — full drug profile →

Conditions studied

• Chronic Lymphocytic Leukemia — all drugs for Chronic Lymphocytic Leukemia →
• Small Lymphocytic Lymphoma — all drugs for Small Lymphocytic Lymphoma →

Sponsor

Jeanette Lundin

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. The Role of Bruton's Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions.
   Robak T, Witkowska M, Smolewski P. · · 2022 · cited 42× · PMID 35159041 · DOI 10.3390/cancers14030771
2. Targeting ITK signaling for T cell-mediated diseases.
   Weeks S, Harris R, Karimi M. · · 2021 · cited 23× · PMID 34368657 · DOI 10.1016/j.isci.2021.102842
3. Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.
   Pang Y, Lu T, Xu-Monette ZY, Young KH. · · 2023 · cited 16× · PMID 36982568 · DOI 10.3390/ijms24065493
4. Ibrutinib's off-target mechanism: cause for dose optimization.
   Zimmerman SM, Peer CJ, Figg WD. · · 2021 · cited 13× · PMID 34632931 · DOI 10.1080/15384047.2021.1980313