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

NCT04771507 | Recruiting Phase 1

• 1 other identifier: HCK-LT-CLL02/2017
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 9

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

Outcome Measures

Primary Outcomes (1)

• Safety measured as type, frequency and severity of adverse events.

  Type, frequency and severity of adverse events and relationship to intermittent ibrutinib dosing.

  Through study completion, 1-24 months.

Secondary Outcomes (8)

• Overall response at each treatment cycle.

  Through study completion, 1-24 months.

• Time to PR and PR-L at each cycle.

  Through study completion, 1-24 months.

• Time to stop until restart of ibrutinib due to progress

  Through study completion, 1-24 months.

• Number of ibrutinib treatment cycles and OFF therapy periods.

  Through study completion, 1-24 months.

• Cumulative dose of ibrutinib.

  Through study completion, 1-24 months.

Study Arms (1)

Intermittent ibrutinib

EXPERIMENTAL

Intermittent treatment with ibrutinib.

Drug: Ibrutinib

Interventions

Ibrutinib 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.

Also known as: Imbruvica

Intermittent ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jeanette Lundin: lead

Study Sites (9)

St Olavs Hospital

Trondheim, 7030, Norway

RECRUITING

Falu lasarett

Falun, Dalarna County, 791 82, Sweden

RECRUITING

Gävle Hospital

Gävle, Gävleborg County, 801 87, Sweden

RECRUITING

Skåne University Hospital

Lund, Skåne County, 222 42, Sweden

NOT YET RECRUITING

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

NOT YET RECRUITING

Örebro University Hospital

Örebro, 701 85, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, 17176, Sweden

RECRUITING

Norrland's University Hospital

Umeå, 901 85, Sweden

NOT YET RECRUITING

Akademiska hospital

Uppsala, 751 85, Sweden

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jeanette Lundin, MD PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeanette Lundin, MD PhD

CONTACT

0700 85 67 86; jeanette.lundin@sll.se

Sanna Nyström, PhD

CONTACT

08 517 759 27; sanna.nystrom@sll.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant, Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 25, 2021
• Study Start: February 23, 2018
• Primary Completion: April 1, 2023
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 25, 2021

Record last verified: 2021-02

Locations

SE (8); NO (1)