Clinical Trials /

Oral Tazemetostat in Combination With Rituximab in R/R FL

NCT04590820

Description:

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

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Oral Tazemetostat in Combination With Rituximab in R/R FL
  • 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: EPZ-6438-007-2019
  • NCT ID: NCT04590820

Conditions

  • Follicular Lymphoma
  • Non Hodgkin Lymphoma
  • Lymphoma

Interventions

DrugSynonymsArms
TazemetostatEPZ-6438Tazemetostat + Rituxan
RituximabRituxanTazemetostat + Rituxan

Purpose

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

Detailed Description

      Tazemetostat 800 mg BID is administered daily starting on Cycle 1 Day 1. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Tazemetostat + RituxanExperimentalTazemetostat 800 mg BID is administered daily starting on Cycle 1 Day 1. Rituximab will be administered by either Subcutaneous injection or IV infusion 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.
  • Tazemetostat
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          1. Men and women of 18 years of age and older

          2. Voluntary agreement to provide written informed consent and the willingness and
             ability to comply with all aspects of the protocol.

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

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

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

               -  Any nodal or extranodal tumor mass >7 cm diameter

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

               -  Presence of any systemic or B symptoms

               -  Splenic enlargement with inferior margin below the umbilical line

          6. Compression syndrome (ureteral, orbital, gastrointestinal)

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

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

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

         10. Meet the following laboratory parameters:

               -  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

               -  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.

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

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

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

         11. No prior therapy with EZH2 inhibitors

         12. 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

               -  Previously irradiated lesions should not be counted as target lesions

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

               -  Bone lesions should not be counted as target lesions

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

         14. Female subjects of reproductive potential must have a negative urine/serum\ pregnancy
             test upon study entry. Female subjects who are of non-reproductive potential (ie,
             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.

         15. 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.

         16. 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:

               -  Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin

               -  Curatively treated carcinoma in situ of the cervix

               -  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:

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

               -  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:Evaluate Objective response rate
Time Frame:4 years
Safety Issue:
Description:To determine the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab

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: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 progression-free survival (PFS) rate of tazemetostat in combination with rituximab at 2 years

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Swedish Medical Center

Trial Keywords

  • relapsed
  • refractory

Last Updated

October 14, 2020