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JOURNAL ONKOLOGIE – STUDIE
SYMPHONY-1

Study of Tazemetostat Versus Placebo When Given in Combination With Lenalidomide and Rituximab in Participants With Relapsed/Refractory Follicular Lymphoma

Rekrutierend

NCT-Nummer:
NCT04224493

Studienbeginn:
Juni 2020

Letztes Update:
19.04.2024

Wirkstoff:
Tazemetostat, Placebo Oral Tablet

Indikation (Clinical Trials):
Lymphoma, Lymphoma, Follicular

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Epizyme, Inc.

Collaborator:
-

Studienleiter

Ipsen Medical Director
Study Director
Ipsen

Kontakt

Studienlocations
(3 von 162)

Klinikum rechts der Isar der Technischen Universitat Muenche
81675 München
(Bayern)
GermanyZurückgezogen» Google-Maps
TOI - Clinical Research
90703 Cerritos
United StatesRekrutierend» Google-Maps
SCL Health Lutheran Medical Center
80033 Greeley
United StatesZurückgezogen» Google-Maps
Mayo Clinic - Cancer Clinical Research Office
32224 Jacksonville
United StatesZurückgezogen» Google-Maps
Miami Cancer Institute
33176 Miami
United StatesZurückgezogen» Google-Maps
Florida Cancer Specialists - Panhandle
32308 Tallahassee
United StatesRekrutierend» Google-Maps
Kaiser Permanente Hawaii Moanalua Medical Center
96819 Honolulu
United StatesZurückgezogen» Google-Maps
The University of Kansas Cancer Center
66210 Overland Park
United StatesZurückgezogen» Google-Maps
University of Maryland
21201 Baltimore
United StatesZurückgezogen» Google-Maps
The office of Frederick P. Smith, MD, P.C.
20815-6908 Chevy Chase
United StatesZurückgezogen» Google-Maps
Mass General Cancer Center at Newton-Wellesley
02462 Newton
United StatesZurückgezogen» Google-Maps
Hackensack University Medical John Theurer Cancer Center
07601 Hackensack
United StatesZurückgezogen» Google-Maps
Regional Cancer Care Associates LLC - Howell
07731 Howell
United StatesZurückgezogen» Google-Maps
New York Oncology Hematology, P.C.
12206 Albany
United StatesZurückgezogen» Google-Maps
Memorial Sloan-Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
Levine Cancer Institute - Concord
28205 Concord
United StatesRekrutierend» Google-Maps
University of Pittsburgh Medical Center - Oncology
15232 Pittsburgh
United StatesZurückgezogen» Google-Maps
Western Pennsylvania Hospital Hematology & Cellular Therapy
15524 Pittsburgh
United StatesRekrutierend» Google-Maps
Tennessee Oncology, PLLC
37404 Chattanooga
United StatesZurückgezogen» Google-Maps
The University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
Peninsula Cancer Institute
23320 Chesapeake
United StatesZurückgezogen» Google-Maps
MC Rockwood Cancer Bl Specialty Ctr - North
99218 Spokane
United StatesZurückgezogen» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed 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.

Ein-/Ausschlusskriterien

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: Patients 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. Patients seropositive for

HBV with undetectable HBV DNA by PCR are permitted with appropriate antiviral

prophylaxis.

- Negative test results for hepatitis C virus (HCV) Note: Patients 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 [β-hCG] tests with a minimum sensitivity of

25 mIU/mL or equivalent units of β-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.

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 (Appendix 3).

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: Patients 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 patient'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.

Studien-Rationale

Primary outcome:

1. Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2) (Time Frame - Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 will be selected at the end of Phase 1b):
The safety and tolerability of tazemetostat in combination with R2 in subjects with R/R FL will be evaluated. RP3D of tazemetostat for further evaluation in phase 3 will be selected as assessed by the occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs).

2. Progression-free Survival (PFS) (Time Frame - Up to 72 months):
PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by Investigators.

Secondary outcome:

1. Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax). (Time Frame - In cycles 1 and 2 on days 1 and 15 (28 days cycle)):
Cmax will be recorded from the PK blood samples collected.

2. PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax) (Time Frame - In cycles 1 and 2 on days 1 and 15 (28 days cycle))

3. 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)], (Time Frame - In cycles 1 and 2 on days 1 and 15 (28 days cycle))

4. PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)] (Time Frame - In cycles 1 and 2 on days 1 and 15 (28 days cycle))

5. The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit (Time Frame - In cycles 1 and 2 on days 1 and 15 (28 days cycle))

6. PFS (Time Frame - Up to 72 months):
PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by blinded independent review committee (IRC).

7. Objective Response Rate (ORR) (Time Frame - Up to 72 months):
ORR is defined as the proportion of subjects achieving partial response (PR) or complete response (CR) according to the 2014 Lugano Classification as assessed by Investigator and IRC.

8. Duration of response (DOR) (Time Frame - Up to 72 months):
DOR is defined as the time from initial CR or PR to documented progression or death, whichever occurs first, as assessed by Investigator and IRC.

9. Duration of complete response (DOCR) (Time Frame - Up to 72 months):
DOCR, defined as the time from initial CR to documented progression or death, whichever occurs first, as assessed by Investigator and IRC.

10. Disease control rate (DCR) (Time Frame - Up to 72 months):
Disease control rate defined as the proportion of subjects with best overall response of CR, PR, or SD lasting 12 or more months, as assessed by the Investigators and IRC.

11. Quality of life questionnaires evaluation (Time Frame - Measured at Screening, on Day 1 and Day 15 of Cycles 1 and 2, on Day 1 and optionally on Day 15 of each cycle from Cycle 3 and beyond, and at end of treatment visit, up to 3 years. (Each cycle is 28 days)):
Evaluate and compare health-related quality of life as measured by the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) instrument and the Functional Assessment of Cancer Therapy -Lymphoma (FACT-Lym)

12. Overall Survival (OS) (Time Frame - up to 100 weeks):
OS is defined as the time from the date of randomization until death due to any cause.

13. Population PK parameters of oral clearance (CL/F) of tazemetostat (Time Frame - Up to 72 months):
CL/F will be used to generate estimates of tazemetostat AUC

14. Population PK parameters of oral volume of distribution (Vd/F) of tazemetostat. (Time Frame - Up to 72 months)

15. Population PK parameters of first-order absorption rate constant (Ka) for tazemetostat. (Time Frame - Up to 72 months)

16. Percentage of Participants Experiencing Adverse Events (AEs) (Time Frame - Up to 72 months):
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

17. Percentage of Participants with Clinically Significant Changes in Physical Examination (Time Frame - Up to 72 months):
Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.

18. Percentage of Participants with Clinically Significant Changes in Vital Signs (Time Frame - Up to 72 months):
Percentage of participants with clinically significant changes in vital signs findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.

19. Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings (Time Frame - Up to 72 months):
Percentage of participants with clinically significant changes in ECG Readings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.

20. Performance status evaluated by Eastern Cooperation Oncology Group (ECOG) (Time Frame - Up to 72 months):
ECOG is a 6-point performance status scale used to assess performance using PA as a key indicator (e.g., 0 = fully active, 2 = up and about more than 50% of walking hours, 5 = dead) Performance status will be assessed per usual clinical practice and will be recorded in the medical record.

21. Duration of Study Drug Exposure (Time Frame - Up to 72 months):
Duration of exposure to study drug will be reported.

22. Total Number of Treatment Cycles (Time Frame - Up to 72 months):
Total number of treatment cycles for the study drug will be reported.

23. Percentage of Study Drug Taken by Participants (Time Frame - Up to 72 months)

24. Average Dose Intensity of Study Drug (Time Frame - Up to 72 months):
The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).

25. Number of Participants Requiring Dose Reductions, Treatment Interruption or Treatment Discontinuation (Time Frame - Up to 72 months)

Studien-Arme

  • Experimental: Tazemetostat + R2 arm
    Stage 1 (Phase 1b): Tazemetostat will be 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 and Optional Stage 3 (Phase 3): 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 (Stage 1, 2, and Optional Stage 3): 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 and Optional Stage 3 (Phase 3): 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 1, 2, and Optional Stage 3): 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.

Geprüfte Regime

  • Tazemetostat (EPZ-6438 / IPN60200 / ):
    Stage 1 (Phase 1b): Tazemetostat will be 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.
  • Tazemetostat (EPZ-6438 / IPN60200 / ):
    Stage 2 and Optional Stage 3 (Phase 3): 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.
  • Placebo oral tablet:
    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.
  • 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.
  • 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.

Quelle: ClinicalTrials.gov


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