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Oral Tazemetostat in Combination With Rituximab in R/R FL

Sponsor
Swedish Medical Center (Other)
Overall Status
Terminated
CT.gov ID
NCT04590820
Collaborator
Epizyme, Inc. (Industry)
2
Enrollment
3
Locations
1
Arm
2.4
Actual Duration (Months)
0.7
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
2 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Open label, non randomized, single armOpen label, non randomized, single arm
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Open-Label, Multicenter Trial of Oral Tazemetostat in Combination With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma
Actual Study Start Date :
Nov 17, 2020
Actual Primary Completion Date :
Jan 29, 2021
Actual Study Completion Date :
Jan 29, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tazemetostat + Rituxan

Tazemetostat 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.

Drug: Tazemetostat
tazemetostat is an oral, small molecule selective and S-adenosyl methionine (SAM) competitive inhibitor of histone methyl transferase EZH2.
Other Names:
  • EPZ-6438

    • Drug: Rituximab
    Rituximab is a chimeric monoclonal antibody against the protein CD20. Given either Intravenous or subcutaneous.
    Other Names:
  • Rituxan

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Evaluate Objective response rate [4 years]

      To determine the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab

    Secondary Outcome Measures

    1. Incidence of Treatment-Emergent Adverse Events [Adverse events will be collected beginning at screening and then at all subsequent time points up to 4 years]

      This will be measured in accordance to National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.00

    2. Progression Free Survival [2 years]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. Compression syndrome (ureteral, orbital, gastrointestinal)

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

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

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

    5. 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.

    1. No prior therapy with EZH2 inhibitors

    2. 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

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

    2. 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.

    3. 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.

    4. 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

    1. 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

    2. 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

    1. Females who are currently breastfeeding

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

    3. Participation in a separate investigational therapeutic study

    4. Psychiatric illness/social situations that would interfere with study compliance

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Swedish Cancer Institute Edmonds Campus Edmonds Washington United States 98026
    2 Swedish Cancer Institute Issaquah Campus Issaquah Washington United States 98029
    3 Swedish Medical Center Cancer Institute - First Hill Seattle Washington United States 98104

    Sponsors and Collaborators

    • Swedish Medical Center
    • Epizyme, Inc.

    Investigators

    • Principal Investigator: Krish Patel, MD, Swedish Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Swedish Medical Center
    ClinicalTrials.gov Identifier:
    NCT04590820
    Other Study ID Numbers:
    • EPZ-6438-007-2019
    First Posted:
    Oct 19, 2020
    Last Update Posted:
    Mar 3, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Swedish Medical Center
    relapsed
    refractory
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Follicular
    Rituximab

    Study Results

    No Results Posted as of Mar 3, 2021