Study in Subjects With Relapsed/Refractory Follicular Lymphoma

  • STATUS
    Recruiting
  • End date
    Dec 29, 2024
  • participants needed
    518
  • sponsor
    Epizyme, Inc.
Updated on 29 January 2021

Summary

This is a multicenter, double-blind, active-controlled, randomized, 3-stage, biomarker enrichment design featuring early futility stopping and sample-size re-estimation with safety run-in designed to evaluate the efficacy and safety of tazemetostat in combination with R2 in subjects with R/R FL, who have completed at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy.

Description

Stage 1 is a safety run-in phase, stage 2 is an efficacy and safety phase for an assessment of the EZH2 Mutant Type population and overall FL population regardless of EZH2 mutation status, and optional stage 3 with efficacy and safety phase for subjects with EZH2 mutation. Stage 3 with Mutant Type population alone will be executed in case the efficacy of the overall population in stage 2 fails whilst the efficacy of EZH2 Mutant Type is sufficiently promising. Stage 2 will include 2 futility interim analyses based on ORR for the first futility and PFS for the second one. In addition, there is a possible sample size re-estimation based on PFS. This is to ensure early detection of the presence/absence of clinical efficacy benefit as well as ensuring adequate powering based on the trial results to demonstrate a meaningful efficacy difference.

Details
Condition Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma
Treatment Rituximab, Lenalidomide, Tazemetostat, Placebo Oral Tablet
Clinical Study IdentifierNCT04224493
SponsorEpizyme, Inc.
Last Modified on29 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have Relapsed/Refractory Follicular Lymphoma?
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Do you have any of these conditions: Do you have Relapsed/Refractory Follicular Lymphoma??
Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol
Males or females are 18 years of age at the time of providing voluntary written informed consent
Life expectancy 3 months before enrollment
Subjects with a history of hepatitis B or C are eligible on the condition that subjects have adequate liver function as defined by Inclusion Criterion #15 and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA
Have histologically confirmed FL, grades 1 to 3A
Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy
Systemic therapy includes treatments such as
Rituximab monotherapy ii. Chemotherapy given with or without rituximab iii. Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab
Systemic therapy does not include, for example: i. Local involved field radiotherapy for limited-stage disease ii. Helicobacter pylori eradication Prior investigational therapies will be allowed provided the subject has received at least
prior systemic therapy as discussed in Inclusion Criteria #6a. 7. Must have
documented relapsed, refractory, or PD after treatment with systemic therapy
(refractory defined as less than PR or disease progression <6 months after
last dose)
\. Have measurable disease as defined by the Lugano Classification (Cheson
)
Time between prior anticancer therapy and first dose of tazemetostat as
follows
Cytotoxic chemotherapy - At least 21 days
Noncytotoxic chemotherapy (eg, small molecule inhibitor) - At least 14 days
Nitrosoureas - At least 6 weeks
Monoclonal antibody(ies) - At least 28 days
Radiotherapy -At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation. 13. Adequate renal function defined as calculated creatinine clearance 40 mL/minute per the Cockcroft and Gault formula or local institutional standard formula
Adequate renal function defined as calculated creatinine clearance 40 mL/minute per the Cockcroft and Gault formula or local institutional standard formula
Adequate bone marrow function. 12. Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of -hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study treatment. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutively amenorrhoeic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing)
Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to randomization, during treatment cycles, and for 30 days after the final dose of study treatment, and have a male partner who uses a condom. Highly effective contraception includes
Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide
Placement of an intrauterine device
Established hormonal contraceptive methods: oral, injectable, or implant. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation
NOTE: Female subjects exempt from this requirement are subjects who practice
total abstinence or have a male partner who is vasectomized. If currently
abstinent, the subject must agree to use a highly effective method of
contraception as described above if they become sexually active during
treatment cycles, and for 30 days after study drug discontinuation. 14. All
study participants enrolled must be registered into the mandatory Revlimid
REMS program and be willing and able to comply with the requirements of the
Revlimid REMS program as appropriate for the country in which the drug is
being used
Female subjects of childbearing potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program. Female subjects exempt from this requirement are subjects who have been in natural menopause for at least 2 years OR have had both ovaries and/or uterus removed
Male subjects must have had either a successful vasectomy OR they and their female partner must meet the criteria above (ie, not of childbearing potential OR practicing highly effective contraception and use a condom throughout the study period and for 30 days after study drug discontinuation)

Exclusion Criteria

All Subjects
Prior exposure to tazemetostat or other inhibitor(s) of EZH2
Prior exposure to lenalidomide for the treatment of FL
Subjects who have mixed or transformed histology
Has thrombocytopenia, neutropenia, or anemia of grade 3 (per CTCAE Version 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)
Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL)
Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases
Subjects taking medications that are known potent cytochrome P450 (CYP)3A4 inducers/inhibitors (including St. John's wort) (Flockhart, 2007; U. S. Food and Drug Administration, February 2015)
Are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from their diet
Major surgery within 4 weeks before the first dose of study drug
Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment
Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat
Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia
Prolongation of corrected QT interval using Fridericia's formula (QTcF) to >480 msec at screening or history of long QT syndrome
Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat
whereas subjects greater than 3 months since deep vein thrombosis/pulmonary embolism are eligible but recommended to receive prophylaxis
Have an active infection requiring systemic therapy
Known hypersensitivity to any component of tazemetostat, lenalidomide, or rituximab
Inability to be treated with a Pneumocystis prophylaxis medication
Have an active infection with hepatitis B virus (as measured by positive hepatitis B surface antigen), HCV (as measured by positive hepatitis C antibody), human immunodeficiency virus, OR human T-cell lymphotropic virus 1
Exceptions: Subjects with a history of hepatitis B or C who have normal ALT AND are hepatitis B surface antigen negative and/or have undetectable HCV RNA
Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study
Female subjects who are pregnant or breastfeeding
Subjects who have undergone a solid organ transplant
Subjects with malignancies other than FL. a. Exception: Subjects with another malignancy who have been disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
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