LEVERAGE

LEVERAGE

Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma

Disease:

Treatment-Naïve Follicular Lymphoma

Summary:

The trial will investigate the combination of venetoclax, obinutuzumab and lenalidomide in patients with treatment-naïve follicular lymphoma.

Patients will receive induction treatment for 0.5 years with venetoclax, obinutuzumab and lenalidomide followed by maintenance treatment for upto 2 years. Maintenance treatment will be determined by the response at the end of induction. Following completion of treatment patients will be followed up for 3 years after the last patient completes induction treatment.

Eligibility:

Include, but not limited to, the following:

Inclusion Criteria:
1. Patient has provided written informed consent.
2. Patient has histologically confirmed follicular lymphoma WHO grade 1-3A and non-contiguous or bulky (>7cm) stage II and stage III or IV according to Lugano criteria 2014, irrespective of FLIPI score
3. Patient meets ≥1 Groupe d'Etude des Lymphomes Folliculaires (GELF) criterion for treatment.
4. Bi-dimensionally measurable disease, with at least one mass lesion ≥ 2 cm in longest diameter.
5. Male or female age ≥ 18 years at signing consent
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
7. Adequate organ and haematologic function within 10 days prior to registration, as defined in Protocol Eligibility
8. Able to comply with protocol requirements and follow-up procedures.
9. Female patients of childbearing potential (FCBP) and males must be willing to comply with birth control as defined in Protocol Eligibility
Exclusion Criteria:
1. WHO grade 3B follicular lymphoma, biopsy proven or clinically suspected histologic transformation to diffuse large B-cell lymphoma
2. Known central nervous system lymphoma or leptomeningeal disease.
3. History of other malignancy that could affect compliance with the protocol or interpretation of results *See Protocol Eligibility for more details
4. Has had prior systemic therapy for follicular lymphoma (with the exception of corticosteroid monotherapy to control disease related symptoms).
5. Major surgery or a wound that has not fully healed within 4 weeks prior to registration.
6. Patient is unable to swallow tablets.
7. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of venetoclax or lenalidomide capsules, or put the study outcomes at undue risk.
8. Known hypersensitivity to any of the study drugs or their components (obinutuzumab, L-histidine, L-histidine hydrochloride monohydrate, Trehalose dehydrate, Poloxamer 188), humanized or murine monoclonal antibodies, xanthine oxidase inhibitors or rasburicase.
9. Has received the following agents within 7 days prior to registration:
o Steroid therapy with anti-neoplastic intent (with the exception of ≤7 days of prednisolone or equivalent at doses of ≤100mg daily to control lymphoma symptoms prior to cycle 1 day 1)
o Strong CYP3A inhibitors (See section 7.10.3)
o Strong CYP3A inducers (See section 7.10.3)
o Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days of registration
10. Has a history of stroke or intracranial hemorrhage within 6 months prior to registration.
11. Has a known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment.
12. Requires the use of vitamin K antagonists (because of potential drug-drug interactions that may potentially increase the exposure of warfarin).
13. Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody.
Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to receive prophylactic lamivudine or entecavir and undergo monthly DNA testing during (and for 6 months following completion of) treatment.
14. Receipt of live-virus vaccines within 28 days prior to registration or need for live-virus vaccines at any time during study treatment.
15. Pregnant or lactating, or intending to become pregnant during the study.

Contact person:

Louise Hay
Email louise.hay@health.wa.gov.au
Phone 08 6383 3207


Email
Phone

Principal Investigator:

Assoc Professor Chan Cheah

08 6457 7600

Sponsor:

Peter MacCallum Cancer Centre, Australia

Phase:

Ib/II

Protocol Number:

LEVERAGE

Trial Registration Number:

NCT03980171

Clinical Trials.gov

ANZ Clinical Trial Registry