Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma (LEVERAGE)
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|ClinicalTrials.gov Identifier: NCT03980171|
Recruitment Status : Recruiting
First Posted : June 10, 2019
Last Update Posted : September 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Follicular Lymphoma||Drug: Obinutuzumab Drug: Venetoclax Drug: Lenalidomide||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Open Label, Phase Ib/II Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma|
|Actual Study Start Date :||August 19, 2019|
|Estimated Primary Completion Date :||November 2026|
|Estimated Study Completion Date :||November 2026|
Patients in both dose escalation and dose expansion will receive 6 cycles of induction treatment consisting of obinutuzumab (flat dose of 1000mg) and protocol defined dose levels of venetoclax and lenalidomide.
A flat dose of 1000mg IV will be given every cycle during induction. a cycle is 28 days.During maintenance 1000mg IV will be given every second cycle for upto 2 years.
During dose escalation, the doses for venetoclax can be 400mg daily days 1-10, 800mg daily days 1-10, 400mg daily continuous or 800mg daily continuous. 6 cycles of treatment will be given during induction. Once the recommended phase 2 dose (RP2D) is established that dose will be used in dose expansion. A further 6 cycles of venetoclax will be given during maintenance if required based on response at the end of induction.
During dose escalation, the doses of lenalidomide can be 15mg for days 1-21 or 20mg for days 1-21. 6 cycles of treatment will be given during induction. During maintenance the dose of lenalidomide will be 10mg continuous for a further 6 cycles if required based on response at the end of induction.
Other Name: Revlimid
- Dose limiting toxicities (DLT) [ Time Frame: During the first 2 cycles of induction during dose escalation which is expected to be completed in 1.5 years. ]A toxicity that prevents further administration of the trial treatment at that dose level.
- Recommended phase II dose (RP2D) of venetoclax in combination with lenalidomide and obinutuzumab [ Time Frame: During dose escalation (1.5 years) ]The highest dose level at which the incidence of DLT was less than 2/6
- Complete response (CR) at the end of induction [ Time Frame: 3.5 years from first patient commencing treatment ]Investigator assessed CR rate by PET-CT after induction (end of cycle 6) by 2014 Lugano criteria
- Adverse events (AEs) of venetoclax, lenalidomide and obinutuzumab [ Time Frame: From signing consent until after completion of study treatment (6.75 years) ]Type, grade and relationship to treatment of AEs, assessed according to Common Terminology of Coding of Adverse Events (CTCAE) v5.0.
- Rate of treatment-emergent AEs that require discontinuation or dose modification of study drug [ Time Frame: From signing consent until after completion of study treatment (6.75 years) ]Type and grade of treatment-emergent AEs, assessed according to CTCAE v5.0, requiring discontinuation of study drug or dose reductions or interruptions
- Overall response rate (ORR) [ Time Frame: 3.5 years from first patient commencing treatment ]Investigator assessed ORR (complete response (CR) or partial response (PR)) by PET-CT assessed by 2014 Lugano criteria after 6 cycles of induction treatment (0.5 years)
- CR at 2.5 years from commencement of induction treatment [ Time Frame: 5.5 years from first patient commencing treatment ]CR based on 2014 Lugano criteria
- Progression free survival (PFS) [ Time Frame: From commencement of treatment to end of study (6.75 years) ]PFS will be defined as the time from enrolment date to the first date of objectively documented progressive disease (PD) or date of death from any cause. Patients without documented progressive disease and who have not died by the end of the study will be censored at the date of last disease assessment.
- Duration of response (DOR) [ Time Frame: From commencement of treatment to end of study (6.75 years) ]DOR will be measured in the subset of patients who achieved CR or PR and it is defined as the time from the first documented disease response to the earliest recurrence or progressive disease. Deceased patients without recurrence or progressive disease will be censored at the date of death.
- Time to next anti-lymphoma treatment (TTNT) [ Time Frame: From commencement of treatment to end of study (6.75 years) ]TTNT will be measured from enrolment date to date of initiation of next anti-cancer therapy (for follicular lymphoma) or date of death from any cause. Patients who do not start next anti-cancer therapy by the end of the study will be censored at the date of last contact.
- Overall survival (OS) [ Time Frame: From commencement of treatment to end of study (6.75 years) ]OS will be measured from enrolment date to the date of death from any cause. Patients who have not died by the study close-out date will be censored at their last visit date. Patients who are lost to follow-up before the close-out date and who are not known to have died will be censored at the date they were last known to be alive.
- Quality of life (QoL) [ Time Frame: From commencement of treatment to end of treatment (5.5 years) ]
QoL will be measured using Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym).
The FACT-Lym is a disease-specific 42-item questionnaire that has been validated for the purpose of assessing health-related quality of life (HRQoL) in patients with various forms of lymphoma.The FACT-Lym consists of FACT-G subscales: Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), Functional Well-Being (7 items), and the Lymphoma subscale: Additional Concerns (15 items). FACT-Lym questions are scored on a 5-point Likert scale from 0 to 4 (0 being not at all and 4 being very much).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03980171
|Contact: John Seymour, MBBS, FRACP, PhD||+613 855 97262||John.Seymour@petermac.org|
|Contact: Chan Y Cheah, MBBS(Hons),DMedSc,FRACP,FRCPA||+618 645 firstname.lastname@example.org|
|United States, Texas|
|The University of Texas MD Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Contact: Nathan Fowler 713-792-2860 email@example.com|
|Peter MacCallum Cancer Centre||Not yet recruiting|
|Melbourne, Victoria, Australia, 3000|
|Contact: John Seymour +613 855 97262 John.Seymour@petermac.org|
|Australia, Western Australia|
|Sir Charles Gairdner Hospital||Recruiting|
|Nedlands, Western Australia, Australia, 6009|
|Contact: Chan Cheah +618 6457 7600 Chan.Cheah@health.wa.gov.au|