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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03980171




Registration number
NCT03980171
Ethics application status
Date submitted
5/06/2019
Date registered
10/06/2019

Titles & IDs
Public title
Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma
Scientific title
A Multicenter, Open Label, Phase Ib/II Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma
Secondary ID [1] 0 0
19/45
Universal Trial Number (UTN)
Trial acronym
LEVERAGE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Venetoclax
Treatment: Drugs - Lenalidomide

Experimental: Obinutuzumab+venetoclax+lenalidomide - 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.


Treatment: Drugs: Obinutuzumab
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.

Treatment: Drugs: Venetoclax
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.

Treatment: Drugs: Lenalidomide
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicities (DLT)
Timepoint [1] 0 0
During the first 2 cycles of induction during dose escalation which is expected to be completed in 1.5 years.
Primary outcome [2] 0 0
Recommended phase II dose (RP2D) of venetoclax in combination with lenalidomide and obinutuzumab
Timepoint [2] 0 0
During dose escalation (1.5 years)
Primary outcome [3] 0 0
Complete response (CR) at the end of induction
Timepoint [3] 0 0
3.5 years from first patient commencing treatment
Primary outcome [4] 0 0
Adverse events (AEs) of venetoclax, lenalidomide and obinutuzumab
Timepoint [4] 0 0
From signing consent until after completion of study treatment (6.75 years)
Primary outcome [5] 0 0
Rate of treatment-emergent AEs that require discontinuation or dose modification of study drug
Timepoint [5] 0 0
From signing consent until after completion of study treatment (6.75 years)
Primary outcome [6] 0 0
Overall response rate (ORR)
Timepoint [6] 0 0
3.5 years from first patient commencing treatment
Primary outcome [7] 0 0
CR at 2.5 years from commencement of induction treatment
Timepoint [7] 0 0
5.5 years from first patient commencing treatment
Primary outcome [8] 0 0
Progression free survival (PFS)
Timepoint [8] 0 0
From commencement of treatment to end of study (6.75 years)
Primary outcome [9] 0 0
Duration of response (DOR)
Timepoint [9] 0 0
From commencement of treatment to end of study (6.75 years)
Primary outcome [10] 0 0
Time to next anti-lymphoma treatment (TTNT)
Timepoint [10] 0 0
From commencement of treatment to end of study (6.75 years)
Primary outcome [11] 0 0
Overall survival (OS)
Timepoint [11] 0 0
From commencement of treatment to end of study (6.75 years)
Primary outcome [12] 0 0
Quality of life (QoL)
Timepoint [12] 0 0
From commencement of treatment to end of treatment (5.5 years)

Eligibility
Key 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, defined by:

* Haemoglobin =80g/L
* ANC =1 x 109/L and platelet count =75 x 109/L; unless due to marrow infiltration or hypersplenism (in which case ANC = 0.5 x 109/L and platelets = 50 x 109/L)
* Serum aspartate transaminase (AST) or alanine transaminase (ALT) <2.5 x upper limit of normal (ULN)
* International normalized ratio >1.5 x ULN for patients not receiving therapeutic anticoagulation
* Partial thromboplastin time (PTT) or activated PTT (aPTT) =1.5 x ULN unless due to the presence of an inhibitor (e.g. lupus anticoagulant)
* Bilirubin <2.0 x ULN unless due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin
* Creatinine clearance =50ml/min(Cockcroft-Gault)
8. Able to comply with protocol requirements and follow-up procedures.
9. Female patients of childbearing potential (FCBP) must be willing to use two methods of birth control simultaneously or be surgically sterile, or abstain from heterosexual activity for at least 28 days before starting lenalidomide and for the course of the study through to 18 months after the last dose of obinutuzumab, 28 days after the last dose of lenalidomide and 30 days after the last dose of venetoclax, whichever is longer. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 24 consecutive months (Refer to Appendix 4).
10. Sexually active males must agree to use a condom during sexual contact with a pregnant female or a female of child-bearing potential (FCBP) for the course of the study through to 18 months after the last dose of obinutuzumab, 28 days after the last dose of lenalidomide and 30 days after the last dose of venetoclax, whichever is longer, even if he has undergone a successful vasectomy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.

Patients with a malignancy that has been treated with curative intent may be included provided they remain in remission without treatment for = 2 years prior to enrollment
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:

* 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)
* Strong CYP3A inhibitors (See section 7.10.3)
* Strong CYP3A inducers (See section 7.10.3)
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2026
Actual
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Townsville Hospital and Health Services - Townsville
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Townsville
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
John Seymour, MBBS, FRACP, PhD
Address 0 0
Country 0 0
Phone 0 0
+613 855 97262
Fax 0 0
Email 0 0
John.Seymour@petermac.org
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03980171