Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Oral Tazemetostat in Combination With Rituximab in R/R FL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04590820
Recruitment Status : Terminated (Study was transferred to Epizyme under NCT04762160 and new study number EZH-1401)
First Posted : October 19, 2020
Last Update Posted : March 3, 2021
Sponsor:
Collaborator:
Epizyme, Inc.
Information provided by (Responsible Party):
Swedish Medical Center

Tracking Information
First Submitted Date  ICMJE December 23, 2019
First Posted Date  ICMJE October 19, 2020
Last Update Posted Date March 3, 2021
Actual Study Start Date  ICMJE November 17, 2020
Actual Primary Completion Date January 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2020)
Evaluate Objective response rate [ Time Frame: 4 years ]
To determine the objective response rate (ORR; complete response + partial response [CR + PR]) of Tazemetostat in combination with Rituximab
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2020)
  • 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 ]
    This will be measured in accordance to National Cancer (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.00
  • Progression Free Survival [ Time Frame: 2 years ]
    To estimate progression-free survival (PFS) rate of tazemetostat in combination with rituximab at 2 years
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral Tazemetostat in Combination With Rituximab in R/R FL
Official Title  ICMJE A Phase II Open-Label, Multicenter Trial of Oral Tazemetostat in Combination With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Open label, non randomized, single arm
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Follicular Lymphoma
  • Non Hodgkin Lymphoma
  • Lymphoma
Intervention  ICMJE
  • Drug: Tazemetostat
    tazemetostat is an oral, small molecule selective and S-adenosyl methionine (SAM) competitive inhibitor of histone methyl transferase EZH2.
    Other Name: EPZ-6438
  • Drug: Rituximab
    Rituximab is a chimeric monoclonal antibody against the protein CD20. Given either Intravenous or subcutaneous.
    Other Name: Rituxan
Study Arms  ICMJE 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.
Interventions:
  • Drug: Tazemetostat
  • Drug: Rituximab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 1, 2021)
2
Original Estimated Enrollment  ICMJE
 (submitted: October 14, 2020)
44
Actual Study Completion Date  ICMJE January 29, 2021
Actual Primary Completion Date January 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04590820
Other Study ID Numbers  ICMJE EPZ-6438-007-2019
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Swedish Medical Center
Study Sponsor  ICMJE Swedish Medical Center
Collaborators  ICMJE Epizyme, Inc.
Investigators  ICMJE
Principal Investigator: Krish Patel, MD Swedish Cancer Institute
PRS Account Swedish Medical Center
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP