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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04224493




Registration number
NCT04224493
Ethics application status
Date submitted
12/12/2019
Date registered
13/01/2020

Titles & IDs
Public title
A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.
Scientific title
Symphony-1: A Phase 1b/3 Double-Blind, Randomized, Active-Controlled, 3-Stage, Biomarker Adaptive Study Of Tazemetostat Or Placebo In Combination With Lenalidomide Plus Rituximab In Subjects With Relapsed/Refractory Follicular Lymphoma
Secondary ID [1] 0 0
2019-003333-42
Secondary ID [2] 0 0
EZH-302
Universal Trial Number (UTN)
Trial acronym
SYMPHONY-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Follicular Lymphoma 0 0
Follicular Lymphoma 0 0
Refractory Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tazemetostat
Treatment: Drugs - Tazemetostat
Treatment: Drugs - Placebo oral tablet
Other interventions - Lenalidomide
Other interventions - Rituximab

Experimental: Tazemetostat + R2 arm - Stage 1 (Phase 1b): This phase is now completed.

* Tazemetostat was escalated from a starting dose of 400 mg PO twice daily to 600 mg PO twice daily to 800 mg PO twice daily in 28-day cycles.
* Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
* Lenalidomide 20 mg or 10 mg (if creatinine clearance =60 mL/minute or \<60 mL/minute), administred PO QD on days 1 to 21 for 12 cycles.

Stage 2:

* Tazemetostat 800 mg administered PO twice daily in continuous 28-day cycles.
* Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
* Lenalidomide 20 mg or 10 mg (if creatinine clearance =60 mL/minute or \<60 mL/minute), PO QD on days 1 to 21 for 12 cycles.

Maintenance Therapy (Stages 1 and 2):

Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Placebo comparator: Placebo + R2 Arm - Stage 2:

* Placebo administered PO twice daily in continuous 28-day cycles.
* Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
* Lenalidomide 20 mg or 10 mg (if creatinine clearance =60 mL/minute or \<60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.

Maintenance Therapy (Stage 2):

Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. During maintenance, placebo will be continued until disease progression or unacceptable toxicity, or participant withdraws consent.


Treatment: Drugs: Tazemetostat
Stage 1 (Phase 1b):

Tazemetostat was escalated from a starting dose of 400 mg orally twice daily to 600 mg orally twice daily to 800 mg PO twice daily in 28-day cycles as tolerated in a standard 3 + 3 design. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Treatment: Drugs: Tazemetostat
Stage 2:

Tazemetostat 800 mg administered orally twice daily in continuous 28-day cycles for 12 cycles. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Treatment: Drugs: Placebo oral tablet
Stage 2:

Placebo administered orally twice daily in continuous 28-day cycles. Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Other interventions: Lenalidomide
Lenalidomide 20 mg capsules or 10 mg capsules (if creatinine clearance =60 mL/minute or \<60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.

Other interventions: Rituximab
Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2)
Timepoint [1] 0 0
Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 was selected at the end of Stage 1
Primary outcome [2] 0 0
Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) population
Timepoint [2] 0 0
Stage 2: Up to 72 months
Primary outcome [3] 0 0
PFS in the Intent-to-treat mutant-type (ITT-MT) population
Timepoint [3] 0 0
Stage 2: Up to 72 months
Secondary outcome [1] 0 0
Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax).
Timepoint [1] 0 0
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
Secondary outcome [2] 0 0
PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax)
Timepoint [2] 0 0
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
Secondary outcome [3] 0 0
PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration [AUC(0-t)],
Timepoint [3] 0 0
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
Secondary outcome [4] 0 0
PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-8)]
Timepoint [4] 0 0
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
Secondary outcome [5] 0 0
The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit
Timepoint [5] 0 0
Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
Secondary outcome [6] 0 0
Complete Response Rate (CRR) in ITT-WT population
Timepoint [6] 0 0
Stage 2: Up to 96 months
Secondary outcome [7] 0 0
CRR in ITT-MT population
Timepoint [7] 0 0
Stage 2: Up to 96 months
Secondary outcome [8] 0 0
CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status
Timepoint [8] 0 0
Stage 2: Up to 96 months
Secondary outcome [9] 0 0
Objective Response Rate (ORR) in the ITT-WT population
Timepoint [9] 0 0
Stage 2: Up to 96 months
Secondary outcome [10] 0 0
ORR in the ITT-MT population
Timepoint [10] 0 0
Stage 2: Up to 96 months
Secondary outcome [11] 0 0
ORR in the R/R FL population regardless of mutation status
Timepoint [11] 0 0
Stage 2: Up to 96 months
Secondary outcome [12] 0 0
Overall Survival (OS) in the ITT-WT population
Timepoint [12] 0 0
Stage 2: Up to 96 months
Secondary outcome [13] 0 0
OS in the ITT-MT population
Timepoint [13] 0 0
Stage 2: Up to 96 months
Secondary outcome [14] 0 0
OS in the R/R FL population regardless of mutation status
Timepoint [14] 0 0
Stage 2: Up to 96 months
Secondary outcome [15] 0 0
PFS in the ITT-WT population, assessed by a blinded IRC
Timepoint [15] 0 0
Stage 2: Up to 96 months
Secondary outcome [16] 0 0
PFS in the ITT-MT population, assessed by a blinded IRC
Timepoint [16] 0 0
Stage 2: Up to 96 months
Secondary outcome [17] 0 0
PFS in the R/R FL population regardless of mutation status, assessed by a blinded IRC
Timepoint [17] 0 0
Stage 2: Up to 96 months
Secondary outcome [18] 0 0
PFS in the R/R FL population regardless of mutation status, assessed by the Investigator
Timepoint [18] 0 0
Stage 2: Up to 96 months
Secondary outcome [19] 0 0
Duration Of Response (DOR) in the ITT-WT population
Timepoint [19] 0 0
Stage 2: Up to 96 months
Secondary outcome [20] 0 0
DOR in the ITT-MT population
Timepoint [20] 0 0
Stage 2: Up to 96 months
Secondary outcome [21] 0 0
DOR in the R/R FL population regardless of mutation status
Timepoint [21] 0 0
Stage 2: Up to 96 months
Secondary outcome [22] 0 0
Duration Of Complete Response (DOCR) in the ITT-WT population
Timepoint [22] 0 0
Stage 2: Up to 96 months
Secondary outcome [23] 0 0
DOCR in the ITT-MT population
Timepoint [23] 0 0
Stage 2: Up to 96 months
Secondary outcome [24] 0 0
DOCR in the R/R FL population regardless of mutation status
Timepoint [24] 0 0
Stage 2: Up to 96 months
Secondary outcome [25] 0 0
Disease Control Rate (DCR) in the ITT-WT population
Timepoint [25] 0 0
Stage 2: Up to 96 months
Secondary outcome [26] 0 0
DCR in the ITT-MT population
Timepoint [26] 0 0
Stage 2: Up to 96 months
Secondary outcome [27] 0 0
DCR in the R/R FL population regardless of mutation status
Timepoint [27] 0 0
Stage 2: Up to 96 months
Secondary outcome [28] 0 0
Population PK parameters of oral clearance (CL/F) of tazemetostat
Timepoint [28] 0 0
Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
Secondary outcome [29] 0 0
Population PK parameters of oral volume of distribution (Vd/F) of tazemetostat.
Timepoint [29] 0 0
Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
Secondary outcome [30] 0 0
Population PK parameters of first-order absorption rate constant (Ka) for tazemetostat.
Timepoint [30] 0 0
Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
Secondary outcome [31] 0 0
Percentage of Participants Experiencing Adverse Events (AEs)
Timepoint [31] 0 0
Up to 36 months
Secondary outcome [32] 0 0
Percentage of Participants with Clinically Significant Changes in Physical Examination
Timepoint [32] 0 0
Up to 36 months
Secondary outcome [33] 0 0
Percentage of Participants with Clinically Significant Changes in Vital Signs
Timepoint [33] 0 0
Up to 36 months
Secondary outcome [34] 0 0
Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings
Timepoint [34] 0 0
Up to 72 months
Secondary outcome [35] 0 0
Performance status evaluated by Eastern Cooperation Oncology Group (ECOG)
Timepoint [35] 0 0
Up to 72 months
Secondary outcome [36] 0 0
Duration of Study Drug Exposure
Timepoint [36] 0 0
Up to 36 months
Secondary outcome [37] 0 0
Percentage of study drug taken by participants
Timepoint [37] 0 0
Up to 36 months
Secondary outcome [38] 0 0
Quality of life questionnaires evaluation
Timepoint [38] 0 0
Up to 36 months

Eligibility
Key inclusion criteria
1. Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.
2. Males or females are =18 years of age at the time of providing voluntary written informed consent.
3. Life expectancy =3 months before enrollment.
4. Meet requirement for hepatitis and human immunodeficiency virus (HIV) infection as follows

* Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection Note: Participants whose HBV infection status could not be determined by serologic test results have to be negative for HBV-DNA by PCR to be eligible for study participation. Participants seropositive for HBV with undetectable HBV DNA by PCR are permitted with appropriate antiviral prophylaxis.
* Negative test results for hepatitis C virus (HCV) Note: Participants who are positive for HCV antibody must be negative for HCV RNA by PCR to be eligible for study participation
* If HIV positive, HIV infection is controlled
5. Have histologically confirmed FL, Grades 1 to 3A.
6. Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy:

a. Systemic therapy includes treatments such as:

i. Rituximab monotherapy

ii. Chemotherapy given with or without rituximab

iii. Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I-tositumomab.

b. Systemic therapy does not include, for example:

i. Local involved field radiotherapy for limited-stage disease

ii. Helicobacter pylori eradication

c. Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criterion #6a.

d. Prior autologous/allogeneic hematopoietic stem cell transplant (HSCT) will be allowed.

e. Prior chimeric antigen receptor T-cell therapy (CAR T) will be allowed.
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).
8. Have measurable disease as defined by the Lugano Classification (Cheson, 2014; Appendix 5).
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
10. Within 7 days prior to randomization, all clinically significant toxicity related to a prior anticancer treatment (ie, chemotherapy, immunotherapy, and/or radiotherapy must have either resolved to Grade 1 per NCI CTCAE Version 5.0 OR are clinically stable and no longer clinically significant.
11. Have provided sufficient tumor tissue block or unstained slides for EZH2 mutation testing in all subjects to allow for stratification

a. If EZH2 mutation status is known from site-specific testing, subjects can be enrolled. Tumor tissue will be required for confirmatory testing of EZH2 status at study-specific laboratories. If the archival tumor sample was collected more than 24 months prior to the anticipated administration of the first dose (cycle 1 day 1), then a fresh biopsy must be provided. Fresh tumor biopsy is appropriate except for procedures deemed to result in unacceptable risk because of the anatomical location including brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel. Archival tumor biopsy sections mounted on slides are also acceptable.

NOTE: Confirmatory testing will also be performed for Stage 1, if local EZH2 testing is conducted, unless there is insufficient tumor tissue to perform testing after discussion with the Sponsor's or Designee Medical Monitor.
12. Time between prior anticancer therapy and first dose of tazemetostat as follows:

1. Cytotoxic chemotherapy - At least 21 days.
2. Noncytotoxic chemotherapy (eg, small molecule inhibitor) - At least 14 days.
3. Nitrosoureas - At least 6 weeks.
4. Monoclonal and/or bispecific antibodies or CAR T - At least 28 days.
5. 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 =30 mL/minute per the Cockcroft and Gault formula.
14. Adequate bone marrow function:

a. Absolute neutrophil count (ANC) =1000/mm3 (=1.0 × 10^9/L) if no lymphoma infiltration of bone marrow OR ANC =750/mm3 (=75 × 10^9/L) with bone marrow infiltration
* Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days.

b. Platelets =75,000/mm3 (=75 × 10^9/L)
* Evaluated at least 7 days after last platelet transfusion.

c. Hemoglobin =9.0 g/dL
* May receive transfusion
15. Adequate liver function:

1. Total bilirubin =1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
2. Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =3 × ULN (=5 × ULN if subject has liver infilration).
16. International normalized ratio (INR) =1.5 × ULN and activated partial thromboplastin time (aPTT) =1.5 × ULN (unless on warfarin, then INR =3.0). In subjects with thromboembolism risk, prophylactic anticoagulation, or antiplatelet therapy at investigator discretion is recommended.
17. Females of childbearing potential (FCBP) must have a negative urine or serum pregnancy tests (beta-human chorionic gonadotropin [ß-hCG] tests with a minimum sensitivity of 25 mIU/mL or equivalent units of ß-hCG) at screening within 10 to 14 days prior to first dose of study drug. The subject may not receive study drug until the study doctor has verified that the results of pregnancy tests are negative. All females will be considered to be of childbearing potential unless they are naturally postmenopausal (at least 24 months consecutively amenorrhoeic [amenorrhea following cancer therapy does not rule out childbearing potential] and without other known or suspected cause) or have been sterilized surgically (ie, total hysterectomy and/or bilateral oophorectomy, with surgery completed at least 1 month before dosing).
18. Females of childbearing potential (FCBP) enrolled must either practice complete abstinence or agree to use two reliable methods of contraception simultaneously. This includes ONE highly effective method of contraception and ONE additional effective contraceptive method. Contraception must begin at least 28 days prior to first dose of study drug, continue during study treatment (including during dose interruptions), and for 12 months after study drug discontinuation. Female subjects must also refrain from breastfeeding for 12 months following last dose of study drug. If the below contraception methods are not appropriate for the FCBP, she must be referred to a qualified contraception provider to determine the medically effective contraception method appropriate for the subject. The following are examples of highly effective and additional effective methods of contraception:

Examples of highly effective methods:
* Intrauterine device (IUD)
* Hormonal (ovulation inhibitory combined [estrogen and progesterone] birth control pills or intravaginal/transdermal system, injections, implants, levonorgestrel-releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g. desogestrel]) NOTE: There is a potential for tazemetostat interference with hormonal contraception methods due to enzymatic induction.
* Bilateral tubal ligation
* Partner's vasectomy (if medically confirmed [azoospermia] and sole sexual partner).

Examples of additional effective methods:
* Male latex or synthetic condom,
* Diaphragm,
* Cervical Cap

NOTE: Female subjects of childbearing potential exempt from these contraception requirements are subjects who practice complete abstinence from heterosexual sexual contact. True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
19. All study participants enrolled must be registered into the applicable pregnancy prevention program (e.g. REVLIMID REMS in the US, Pregnancy Prevention Programme [PPP] in Europe, RevAid in Canada) for lenalidomide to be administered and be willing and able to comply with the requirements of the applicable program as appropriate for the country in which the drug is being used.

a. Female subjects of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in theapplicable pregnancy prevention program. During study treatment, FCBP must agree to have pregnancy testing weekly for the first 28 days of study participation and then every 28 days for FCBP with regular or no menstrual cycles OR every 14 days for FCBP with irregular menstrual cycles. FCBP must also have a pregnancy test at end of lenalidomide treatment, at days 14 and 28 following the last dose of lenalidomide and at overall treatment discontinuation (at the End-of-Treatment/30-day safety Follow-up visit). Female subjects exempt from this requirement are subjects who have been naturally postmenopausal for at least 24 consecutive months OR have had a total hysterectomy and/or bilateral oophorectomy.
20. Male subjects must either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy (medically confirmed azoospermia), during sexual contact with a pregnant female or FCBP from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.

NOTE: Male subjects must not donate semen or sperm from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
All Subjects

1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
2. Prior exposure to lenalidomide or drugs of the same class.
3. Grade 3b, mixed histology, or FL that has histologically transformed to diffuse large B-cell lymphoma (DLBCL) (subjects transformed from DLBCL to FL may be enrolled).
4. 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)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).
5. Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL).
6. Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
7. Subjects taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. John's wort).
8. Are unwilling to exclude grapefruit juice, Seville oranges, and grapefruits from the diet and/or consumed within 1 week of the first dose of study drug and for the duration of the study.
9. Major surgery within 4 weeks before the first dose of study drug.

a. Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment.
10. 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.
11. 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.
12. Prolongation of corrected QT interval using Fridericia's formula (QTcF) to =480 msec at screening or history of long QT syndrome.
13. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.

a. Note: Participants who have experienced deep vein thrombosis/pulmonary embolism more than 3 months before enrollment are eligible but are recommended to receive prophylaxis.
14. Have an active infection requiring systemic therapy.
15. Known hypersensitivity to any component of tazemetostat or lenalidomide; known severe hypersensitivity to any component of rituximab requiring hospitalization or resuscitation.
16. Active viral infection with or seropositive for HBV: HBV surface antigen (HBsAg) positive OR HBsAg negative, anti-HBs positive and/or anti-HBc positive with detectable HBV DNA.

NOTE: Subjects who are HBsAg negative, anti-HBs positive and/or anti-HBc positive, but with undetectable viral DNA and normal ALT are eligible. Subjects who are seropositive due to HBV vaccination (HBsAg negative, HBV surface antibody [anti-HBs] positive, and HBV core antibody [anti-HBc] negative) are eligible.
17. Active viral infection with hepatitis C virus (as measured by positive HCV antibody and detectable viral RNA, HIV), or known active infection with human T-cell lymphotropic virus.

NOTE: Subjects with a history of hepatitis C infection (HCV antibody reactive) who have normal ALT and undetectable HCV RNA are eligible.
18. Any other medical or social condition that, in the Investigator's judgment, will interfere with a participant's ability to provide informed consent, to receive study drugs, or meet study demands, or that substantially increases the risk associated with the subject's participation in the study, or that may interfere with interpretation of results.
19. Female subjects who are pregnant or lactating/breastfeeding.
20. Subjects who have undergone a solid organ transplant.
21. Subjects with malignancies other than FL. a. Exception: Subjects with another malignancy who have been disease-free for 3 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2029
Actual
Sample size
Target
612
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Barwon Health, University Hospital Geelong - Geelong
Recruitment hospital [5] 0 0
Hollywood Private Hospital - Nedlands
Recruitment hospital [6] 0 0
GenesisCare - St Andrew's - Adelaide
Recruitment hospital [7] 0 0
Peninsula Health - Frankston - Frankston
Recruitment hospital [8] 0 0
Gold Coast University Hosptial - Southport
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Frankston
Recruitment postcode(s) [8] 0 0
- Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Hawaii
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Utah
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
United States of America
State/province [27] 0 0
Washington
Country [28] 0 0
Belgium
State/province [28] 0 0
Namur
Country [29] 0 0
Belgium
State/province [29] 0 0
Oost-Vlaanderen
Country [30] 0 0
Belgium
State/province [30] 0 0
Vlaams Brabant
Country [31] 0 0
Canada
State/province [31] 0 0
Ontario
Country [32] 0 0
Canada
State/province [32] 0 0
Quebec
Country [33] 0 0
China
State/province [33] 0 0
Fujian
Country [34] 0 0
China
State/province [34] 0 0
Guizhou
Country [35] 0 0
China
State/province [35] 0 0
Hangzhou
Country [36] 0 0
China
State/province [36] 0 0
Hebei
Country [37] 0 0
China
State/province [37] 0 0
Henan
Country [38] 0 0
China
State/province [38] 0 0
Hunan
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China
State/province [39] 0 0
Jinlin
Country [40] 0 0
China
State/province [40] 0 0
Shandong
Country [41] 0 0
China
State/province [41] 0 0
Shanghai
Country [42] 0 0
China
State/province [42] 0 0
Shanxi
Country [43] 0 0
China
State/province [43] 0 0
Beijing
Country [44] 0 0
China
State/province [44] 0 0
Tianjin
Country [45] 0 0
France
State/province [45] 0 0
Aquitaine
Country [46] 0 0
France
State/province [46] 0 0
Bretagne
Country [47] 0 0
France
State/province [47] 0 0
Gironde
Country [48] 0 0
France
State/province [48] 0 0
Haut-Rhin
Country [49] 0 0
France
State/province [49] 0 0
Haute-Normandie
Country [50] 0 0
France
State/province [50] 0 0
Haute-Vienne
Country [51] 0 0
France
State/province [51] 0 0
Isere
Country [52] 0 0
France
State/province [52] 0 0
Loire-Atlantique
Country [53] 0 0
France
State/province [53] 0 0
Nord
Country [54] 0 0
France
State/province [54] 0 0
Sarthe
Country [55] 0 0
France
State/province [55] 0 0
Angers
Country [56] 0 0
France
State/province [56] 0 0
Besancon
Country [57] 0 0
France
State/province [57] 0 0
Caen
Country [58] 0 0
France
State/province [58] 0 0
Clermont-Ferrand
Country [59] 0 0
France
State/province [59] 0 0
Lens
Country [60] 0 0
France
State/province [60] 0 0
Nantes
Country [61] 0 0
France
State/province [61] 0 0
Paris
Country [62] 0 0
France
State/province [62] 0 0
Poitiers
Country [63] 0 0
France
State/province [63] 0 0
Périgueux
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France
State/province [64] 0 0
Vandœuvre-lès-Nancy
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France
State/province [65] 0 0
Vannes
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France
State/province [66] 0 0
Villejuif
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France
State/province [67] 0 0
Île-de-France
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Germany
State/province [68] 0 0
Baden-Württemberg
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Germany
State/province [69] 0 0
Bayern
Country [70] 0 0
Germany
State/province [70] 0 0
Hessen
Country [71] 0 0
Germany
State/province [71] 0 0
Nordrhein-Westfalen
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Germany
State/province [72] 0 0
Schleswig-Holstein
Country [73] 0 0
Hungary
State/province [73] 0 0
Hajdú-Bihar
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Hungary
State/province [74] 0 0
Budapest
Country [75] 0 0
Italy
State/province [75] 0 0
Campania
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Italy
State/province [76] 0 0
Forli-Cesena
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Italy
State/province [77] 0 0
Brescia
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Italy
State/province [78] 0 0
Catania
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Italy
State/province [79] 0 0
Firenze
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Italy
State/province [80] 0 0
Lecce
Country [81] 0 0
Italy
State/province [81] 0 0
Milano
Country [82] 0 0
Italy
State/province [82] 0 0
Monza
Country [83] 0 0
Italy
State/province [83] 0 0
Pescara
Country [84] 0 0
Italy
State/province [84] 0 0
Rimini
Country [85] 0 0
Italy
State/province [85] 0 0
Roma
Country [86] 0 0
Italy
State/province [86] 0 0
Terni
Country [87] 0 0
Italy
State/province [87] 0 0
Torino
Country [88] 0 0
Italy
State/province [88] 0 0
Trieste
Country [89] 0 0
Korea, Republic of
State/province [89] 0 0
Seoul Teugbyeolsi [Seoul-T'ukp]
Country [90] 0 0
Korea, Republic of
State/province [90] 0 0
Seoul Teugbyeolsi [Seoul-T'ukp
Country [91] 0 0
Korea, Republic of
State/province [91] 0 0
Seoul Teugbyeolsi
Country [92] 0 0
Korea, Republic of
State/province [92] 0 0
Busan
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Incheon
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Suwon
Country [95] 0 0
Poland
State/province [95] 0 0
Mazowieckie
Country [96] 0 0
Poland
State/province [96] 0 0
Wielkopolskie
Country [97] 0 0
Poland
State/province [97] 0 0
Katowice
Country [98] 0 0
Poland
State/province [98] 0 0
Kraków
Country [99] 0 0
Poland
State/province [99] 0 0
Slupsk
Country [100] 0 0
Poland
State/province [100] 0 0
Torun
Country [101] 0 0
Poland
State/province [101] 0 0
Warszawa
Country [102] 0 0
Poland
State/province [102] 0 0
Wroclaw
Country [103] 0 0
Spain
State/province [103] 0 0
Cataluny
Country [104] 0 0
Spain
State/province [104] 0 0
Málaga
Country [105] 0 0
Spain
State/province [105] 0 0
Barcelona
Country [106] 0 0
Spain
State/province [106] 0 0
Madrid
Country [107] 0 0
Spain
State/province [107] 0 0
Salamanca
Country [108] 0 0
Spain
State/province [108] 0 0
Sevilla
Country [109] 0 0
Taiwan
State/province [109] 0 0
Hualien City
Country [110] 0 0
Taiwan
State/province [110] 0 0
Kaohsiung
Country [111] 0 0
Taiwan
State/province [111] 0 0
Taichung
Country [112] 0 0
Taiwan
State/province [112] 0 0
Tainan
Country [113] 0 0
Taiwan
State/province [113] 0 0
Taipei
Country [114] 0 0
Turkey
State/province [114] 0 0
Ankara
Country [115] 0 0
Turkey
State/province [115] 0 0
Samsun
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Edinburgh, City Of
Country [117] 0 0
United Kingdom
State/province [117] 0 0
London City
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London, City Of
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Cornwell
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Glasgow
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Middlesex

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Epizyme, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ipsen Clinical Study Enquiries
Address 0 0
Country 0 0
Phone 0 0
See e mail
Fax 0 0
Email 0 0
clinical.trials@ipsen.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
When will data be available (start and end dates)?
Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
Available to whom?
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/members/ourmembers/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04224493