Clinical Trials /

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

NCT03980171

Description:

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.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma
  • Official Title: A Multicenter, Open Label, Phase Ib/II Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 19/45
  • NCT ID: NCT03980171

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
ObinutuzumabGAZYVA, GAZYVAROObinutuzumab+venetoclax+lenalidomide
VenetoclaxABT-199 (A-1195425.0), Venclexta, VenclyxtoObinutuzumab+venetoclax+lenalidomide
LenalidomideRevlimidObinutuzumab+venetoclax+lenalidomide

Purpose

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.

Detailed Description

      This is a phase Ib/II (dose escalation/dose expansion), single-arm multi-centre clinical
      trial of venetoclax plus obinutuzumab and lenalinomide in patients with treatment-naïve
      follicular lymphoma. The trial involves an initial dose escalation phase followed by an
      expansion phase. Patients in both the dose escalation and expansion phases will receive 6
      cycles of induction treatment. After patients finish induction treatment, they will undergo
      PET-CT scan, the results of which will determine further therapy. Patients in CR or SD/PR
      from the PET-CT scan result will receive up to 2 years of maintenance therapy. Patients in PD
      from the PET-CT result will not receive any further study treatment. All patients will be
      followed up for 3 years after the last patient has completed induction treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Obinutuzumab+venetoclax+lenalidomideExperimentalPatients 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.
  • Obinutuzumab
  • Venetoclax
  • Lenalidomide

Eligibility Criteria

        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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:A toxicity that prevents further administration of the trial treatment at that dose level.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Peter MacCallum Cancer Centre, Australia

Last Updated

September 17, 2019