Clinical Trials /

Mosunetuzumab With Lenalidomide Augmentation as First-line Therapy for Follicular and Marginal Zone Lymphoma

NCT04792502

Description:

BrUOG-401 is a prospective, single-arm, phase 2 trial of first-line therapy in adult patients with previously untreated FL or MZL. All patients will be assigned the same initial treatment plan, modified by interim response assessment (IRA) after Cycle 4. All patients will start treatment with four 21-day cycles (C1-4) of mosunetuzumab alone (using step-up dosing during C1), followed by IRA. Patients who achieve CR at IRA will continue with additional 4 cycles (C5-8) of mosunetuzumab. Patients who achieve PR at IRA will receive mosunetuzumab with lenalidomide augmentation during C5-8. Primary response assessment (PRA) will occur after C8. Patients who remain in PR at PRA will continue for additional 4 cycles (extended augmentation).

Related Conditions:
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Mosunetuzumab With Lenalidomide Augmentation as First-line Therapy for Follicular and Marginal Zone Lymphoma
  • Official Title: BrUOG 401: A Phase 2 Study of Mosunetuzumab With Lenalidomide Augmentation as First-line Therapy for Follicular and Marginal Zone Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: BrUOG 401
  • NCT ID: NCT04792502

Conditions

  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • B-cell Lymphoma

Interventions

DrugSynonymsArms
MosunetuzumabPlanned Therapy
LenalidomidePlanned Therapy

Purpose

BrUOG-401 is a prospective, single-arm, phase 2 trial of first-line therapy in adult patients with previously untreated FL or MZL. All patients will be assigned the same initial treatment plan, modified by interim response assessment (IRA) after Cycle 4. All patients will start treatment with four 21-day cycles (C1-4) of mosunetuzumab alone (using step-up dosing during C1), followed by IRA. Patients who achieve CR at IRA will continue with additional 4 cycles (C5-8) of mosunetuzumab. Patients who achieve PR at IRA will receive mosunetuzumab with lenalidomide augmentation during C5-8. Primary response assessment (PRA) will occur after C8. Patients who remain in PR at PRA will continue for additional 4 cycles (extended augmentation).

Trial Arms

NameTypeDescriptionInterventions
Planned TherapyExperimental
  • Mosunetuzumab
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          1. Ability to understand and the willingness to sign a written informed consent document
             and to comply with the study protocol procedures.

          2. Age ≥18 years at the time of signing informed consent. Because no dosing or adverse
             event data are currently available on the use of mosunetuzumab in patients <18 years
             of age, they are excluded from this study.

          3. Histologically confirmed diagnosis of:

               -  follicular lymphoma (grade 1, 2, 3a, or not otherwise specified) or

               -  marginal zone lymphoma (nodal, extranodal, or splenic), according to 2016 WHO
                  classification and confirmed to express the CD20 antigen by immunohistochemistry
                  or flow cytometry. Patients in whom definitive pathologic subtype of FL/MZL is
                  undetermined due to limited biopsy material can be enrolled if in the
                  investigator's opinion integrated clinicopathologic data are consistent with the
                  eligible diagnosis.

          4. Agreement to provide, if available, lymphoma tissue for correlative analyses.

          5. At least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its
             longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as
             >1.0 cm in its longest diameter; with the exception of splenic MZL, which must be
             evaluable using the International SMZL Group criteria.76,88,89

          6. No prior systemic therapy for B-cell lymphoma, except for palliative corticosteroids;
             prior radiation therapy is allowed.

          7. Indication to start systemic therapy for lymphoma, in the investigator's judgement.
             Patients with low burden of disease are eligible if they desire therapy; asymptomatic
             patients should thoroughly understand the risks and benefits of lymphoma-directed
             therapy versus watchful waiting.

          8. Performance status ECOG 0, 1, or 2.

          9. Adequate hematologic function (unless due to underlying lymphoma as established by
             bone marrow involvement or splenomegaly):

               -  hemoglobin ≥9 g/dL,

               -  absolute neutrophil count ≥1.0 x 109/L,

               -  platelet count ≥75 x 109/L.

         10. Glomerular filtration rate (GFR) ≥40 mL/min/1.73m2 using the Mayo Quadratic Formula.

         11. The effects of mosunetuzumab on the developing human fetus are unknown. For this
             reason and because lenalidomide used in this trial is known to be teratogenic, women
             of child-bearing potential and men must agree to use adequate contraception (hormonal
             or barrier method of birth control; abstinence) and refrain from donating eggs or
             sperm throughout the treatment and for 3 months after the last dose of trial therapy.
             Should a woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately.

        Exclusion Criteria:

          1. Grade 3b follicular lymphoma or transformed lymphoma.

          2. Prior treatment with any anti-CD20 antibody or lenalidomide.

          3. Prior stem cell transplantation (autologous or allogeneic) or prior solid organ
             transplantation.

          4. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies or known sensitivity or allergy to murine products.

          5. Known NYHA class 3/4 congestive heart failure, LVEF <40%, myocardial infarction within
             6 months prior to enrollment, unstable angina, or unstable arrhythmia.

          6. Chronic obstructive pulmonary disease (COPD) requiring oral corticosteroids or chronic
             oxygen.

          7. History of autoimmune disease, including, but not limited to myasthenia gravis,
             myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
             syndrome, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple
             sclerosis, vasculitis, or glomerulonephritis, with the exception of: hypothyroidism
             (on stable dose of thyroid replacement therapy), asthma managed with inhaled
             medications only; type 1 diabetes mellitus on stable insulin regimen, Sjögren
             syndrome, immune thrombocytopenia or autoimmune hemolytic anemia that does not require
             systemic therapy; dermatologic condition (including eczema, psoriasis, lichen simplex
             chronicus, or vitiligo) with skin manifestations with rash covering <10% of body
             surface area and not requiring treatment other than low-potency topical
             corticosteroids for >12 months prior to registration.

          8. Use of any systemic immunosuppressive medications (including, but not limited to,
             cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
             factor agents) with the exception of corticosteroid treatment using <10 mg/day
             prednisone or equivalent within 2 weeks prior to first treatment; a brief course of
             palliative corticosteroids at higher doses (prednisone up to 100 mg daily, for up to 7
             days) is allowed, but must be completed at least 7 days before the first dose of
             mosunetuzumab.

          9. Any of the following conditions:

               -  active bacterial infection requiring antibiotics

               -  known or suspected chronic active Epstein Barr virus (CAEBV) infection

               -  history of hemophagocytic lymphohistiocytosis (HLH)

               -  confirmed progressive multifocal leukoencephalopathy (PML)

               -  EBV or CMV viremia

               -  positive test for hepatitis B surface antigen (HBSAg). Patients with a positive
                  total/IgG hepatitis B core antibody (HBcAb) may participate if hepatitis B virus
                  (HBV) DNA is undetectable at screening, if they agree to take entecavir or
                  tenofovir, and undergo periodic DNA testing

               -  positive hepatitis C virus (HCV) antibody, unless a negative polymerase chain
                  reaction (PCR) for HCV is documented

               -  positive test for HIV.

         10. Administration of a live, attenuated vaccine within 4 weeks before first mosunetuzumab
             dose or anticipation that such a live, attenuated vaccine will be required during the
             study.

         11. Current or past history of CNS disease, including stroke, epilepsy, or CNS vasculitis,
             or an advanced neurodegenerative disease; with the exception of: stroke >2 years
             before registration without any residual neurologic deficits and no subsequent
             transient ischemic attacks; history of epilepsy with no seizures for >2 years and not
             using any antiepileptic therapy; well-controlled Parkinson's disease (with no need for
             medication adjustment for >6 months).

         12. History of other malignancy that could affect compliance with the protocol or
             interpretation of results; patients with a curatively treated skin cancer, in situ
             cervical cancer, or another malignancy treated curatively with a documented remission
             >2 years before registration are eligible.

         13. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) at study enrollment or any major episode of
             infection requiring treatment with IV antibiotics or hospitalization within 4 weeks
             before the first dose of mosunetuzumab.

         14. Clinically significant liver disease, including viral or other hepatitis, current
             alcohol abuse, or cirrhosis.

         15. Any major surgery within 4 weeks before the first dose of mosunetuzumab, other than
             lymph node biopsy for diagnosis.

         16. Evidence of other significant or uncontrolled medical or psychiatric conditions that
             could affect compliance with the protocol.

         17. Any of the following abnormal laboratory values within 14 days prior to first dose of
             mosunetuzumab:

               -  AST or ALT >3x ULN

               -  total bilirubin >2 x ULN (unless due to Gilbert syndrome with indirect
                  hyperbilirubinemia only)

               -  INR>1.5 x ULN without anticoagulation

               -  PTT or APTT >1.5x ULN in the absence of lupus anticoagulant.

         18. Any radiation therapy within 2 weeks prior to first dose of mosunetuzumab.

         19. Pregnancy, breast-feeding, or prisoner status. Women of childbearing potential must
             have a negative pregnancy test within 2 weeks before first dose of mosunetuzumab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response Rate
Time Frame:At the end of Cycle 8 (each cycle is 21 days)
Safety Issue:
Description:The rate of complete response at the time of primary response assessment (PRA).

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:Time of study registration through end of follow-up, approximately 5 years.
Safety Issue:
Description:PFS will be determined according to the guidance from the International Working Group. The following events will be counted for PFS: disease progression, disease recurrence, initiation of new line of therapy, or death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Adam Olszewski

Last Updated

March 11, 2021