Clinical Trials /

A Trial to Examine Combination of Tazemetostat and Rituximab for Patients With Recurrent/Refractory Follicular Lymphoma

NCT04762160

Description:

The goal of this study is to examine the feasibility and efficacy of adding the EZH2 inhibitor, tazemetostat, to rituximab, standard second line or beyond therapy as a means to improve disease response.

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial to Examine Combination of Tazemetostat and Rituximab for Patients With Recurrent/Refractory Follicular Lymphoma
  • Official Title: A Phase II Open-Label, Multicenter Trial of Oral Tazemetostat in Combination With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: EZH-1401
  • NCT ID: NCT04762160

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
Tazemetostatrituximab, RituxanTazmetostat in combination with rituximab

Purpose

The goal of this study is to examine the feasibility and efficacy of adding the EZH2 inhibitor, tazemetostat, to rituximab, standard second line or beyond therapy as a means to improve disease response.

Detailed Description

      This is a phase 2, multicenter, open-label study of oral tazemetostat in combination with
      rituximab in subjects with relapsed or refractory (R/R) follicular lymphoma (FL). This study
      is designed to evaluate the safety and efficacy of tazemetostat in combination with rituximab
      in subjects previously treated with at least 2 prior systemic lines of therapy for FL, and
      features early futility stopping to maintain subject safety.
    

Trial Arms

NameTypeDescriptionInterventions
Tazmetostat in combination with rituximabExperimentalTazemetostat 800 mg BID is administered daily starting on Cycle 1 Day 1 (C1D1). Tazemetostat is supplied by Epizyme in pre-counted, appropriately labeled bottles. Tazemetostat will be administered from C1D1 to the end of Cycle 24, for a total of 24 months of therapy. Rituximab will be administered by either subcutaneous injection or IV infusion according to the regional product prescribing information and labeling. Rituximab will be administered at a dose of 375 mg/m2 on Day 1, 8, 15, and 22 of Cycle 1, and then on Day 1 of Cycles 3 through 6, accounting for an additional 4 doses, i.e., a total of 8 doses of rituximab in 6 cycles. Rituximab will be procured by the clinical sites from commercial sources. Disease Assessments will be performed at screening, C3D1, C6D1, C12D1, C18D1, C24D1
  • Tazemetostat

Eligibility Criteria

        Inclusion Criteria:

          1. Have histologically confirmed FL, grades 1 to 3a. Subjects may have
             relapsed/refractory disease following at least 2 standard prior systemic treatment
             regimens where at least an anti-CD20-based regimen was used.

          2. Eastern Cooperative Oncology Group (ECOG) score of 0 </= 2

          3. Treatment recommended in accordance with the GELF criteria due to the presence of at
             least one of the following:

               1. Any nodal or extranodal tumor mass >7 cm diameter

               2. Involvement of at least 3 nodal sites, each with diameter >3 cm

               3. Presence of any systemic or B symptoms

               4. Splenic enlargement with inferior margin below the umbilical line

               5. Compression syndrome (ureteral, orbital, gastrointestinal)

               6. Pleural or peritoneal serous effusion (irrespective of cell content)

               7. Leukemic phase (>5.0 x 109/L circulating malignant cells)

               8. Cytopenias (granulocyte count <1.0 x 109/L and/or platelets <100 x 109/L)

          4. Meet the following laboratory parameters:

               1. ANC ≥ 750 cells/μL (0.75 x 109/L), or ≥ 500 cells/μL (0.50 x 109/L) in subjects
                  with documented bone marrow involvement

               2. Platelet count ≥ 50,000 cells/μL (50 x 109/L), or ≥ 30,000 cells/μL (30 x 109/L)
                  in subjects with documented bone marrow involvement, and without transfusion
                  dependence.

               3. Serum AST and ALT/SGPT ≤ 3.0 x ULN, unless related to disease involvement

               4. Total bilirubin ≤ 1.5 x ULN, unless due to disease involvement, Gilbert's, or
                  hemolytic anemia).

               5. Estimated creatinine clearance (ie, eGFR using Cockcroft-Gault) ≥ 40 mL/min.

          5. No prior therapy with EZH2 inhibitors

          6. At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter
             by CT scan or MRI excluding lesions that meet the following criteria

               1. Previously irradiated lesions should not be counted as target lesions

               2. Lesions that are intended to be used to collect tissue samples for biopsy should
                  not be counted as target lesions

               3. Bone lesions should not be counted as target lesions

          7. All clinically significant treatment-related toxicity from prior therapy, except for
             alopecia, resolved to ≤ Grade 1 or to a new stable baseline

          8. Female subjects of reproductive potential must have a negative urine/serum/pregnancy
             test upon study entry. Female subjects who are of non-reproductive potential (i.e.,
             post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR
             history of bilateral tubal ligation; OR history of bilateral oophorectomy) are exempt
             from pregnancy testing.

          9. Male and female subjects of reproductive potential who agree to use both a highly
             effective method of birth control (eg, implants, injectables, combined oral
             contraceptives, some intrauterine devices [IUDs], complete abstinence1, or sterilized
             partner) and a barrier method (eg, condoms, cervical ring, sponge, etc) during the
             period of therapy and for 12 months after the last dose of rituximab.

         10. Men and women must agree to refrain from sperm or oocyte donation during the study and
             for 12 months after the last dose of rituximab.

        Exclusion Criteria:

          1. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia

          2. Transformed Follicular lymphoma

          3. Any uncontrolled illness including, but not limited to, significant active infections,
             hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction

          4. Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B
             core antibody plus have a hepatitis B polymerase chain reaction (PCR) assay (subjects
             with a negative PCR assay are permitted with appropriate anti-viral prophylaxis)

          5. Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV)
             antibody; subjects with positive hepatitis C antibody are eligible if they are
             negative for hepatitis C virus by PCR

          6. Other diagnosis of cancer that is likely to require treatment in the next 2 years,
             with the exception of the following:

               1. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin

               2. Curatively treated carcinoma in situ of the cervix

               3. Hormonal therapy for prostate cancer

          7. History of clinically significant cardiovascular abnormalities such as congestive
             heart failure (New York Heart Association classification ≥ 2), myocardial infarction
             within 6 months of study entry

          8. History of clinically significant gastrointestinal (GI) conditions, particularly:

               1. Known GI condition that would interfere with swallowing or the oral absorption or
                  tolerance of study drug

               2. Pre-existing malabsorption syndrome or other clinical situation that would affect
                  oral absorption

          9. Females who are currently breastfeeding

         10. Received a live virus vaccination within 28 days of first dose of Rituxan

         11. Participation in a separate investigational therapeutic study

         12. Psychiatric illness/social situations that would interfere with study compliance
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Objective Response Rate (ORR)
Time Frame:Screening
Safety Issue:
Description:To assess the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab in patients with relapsed/refractory follicular lymphoma and without EZH2 mutation status

Secondary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:Adverse events will be collected beginning at screening and then at all subsequent time points up to 4 years
Safety Issue:
Description:To evaluate safety of the combination ofTazemetostat and Rituxanby assessingincidence of adverse events/serious adverse events, change of vital signs, lab results, and physical exam findings from baseline. This will be measured in accordance to National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.00
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:To estimate the median progression-free survival (PFS) of tazemetostat in combination with rituximab at 2 years in R/R follicular lymphoma with wild type mutation status, and in the pooled group regardless of mutation status.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Epizyme, Inc.

Trial Keywords

  • follicular lymphoma
  • relapse follicular lymphoma
  • refractory follicular lymphoma
  • rituximab
  • tazemetostat

Last Updated

February 21, 2021