Clinical trial NCT04224493: 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.
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Relapsed/Refractory Follicular Lymphoma
Follicular Lymphoma
Refractory Follicular Lymphoma
Keywords: Epizyme
Tazverik
Tazemetostat (EPZ-6438)
Lenalidomide
Revlimid
Rituximab
Rituxan
Follicular lymphoma
EZH2
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 612
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3 stages study:

Stage 1:

Open-Label (Phase 1b: Safety run-in): All participants will receive Tazemetostat in combination with Lenalidomide and Rituximab

Stage 2:

Double-blinded (Phase 3):

* Study drug arm: Tazemetostat in combination with Lenalidomide and Rituximab
* Placebo arm: Placebo in combination with Lenalidomide and Rituximab

Stage 3:

Long-term Follow-up of participants in Stage 2 after treatment for response, when applicable, and overall survival for up to 5 years after the enrollment of the last patient in the study.
Primary purpose: TREATMENT

Brief summary: The participants of this study would have relapsed/refractory follicular lymphoma.

Follicular lymphoma is a type of blood cancer. It is referred to as 'relapsed' when the disease has come back after a period of improvement after that follows a treatment regimen and 'refractory' when treatment no longer works.

Stage 1 of this trial will study the safety and the level that adverse effects of each of the study drug combinations can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for stage 2 and 3. Stage 1 of the study is completed.

Stages 2 and 3 will evaluate and compare how long participants live without their disease getting worse when receiving the study drug in combination with other drug treatment versus the placebo (dummy drug) in combination with other drug treatment.

Detailed description: Stage 1 is a safety run-in phase, was designed to evaluate the safety of the combination of tazemetostat and R2, as well as to establish the RP3D for Stage 2, which is now completed.

Stage 2 is an efficacy and safety phase for an assessment of the FL population with the enhancer of zeste homolog 2 (EZH2) gain-of-function (GOF) mutation (EZH2 mutant-type \[MT\]) and without the EZH2 GOF mutation (EZH2 wild-type \[WT\]). In Stage 2, EZH2 WT and EZH2 MT patients will be randomly assigned in a 1:1 ratio to tazemetostat + R2 or placebo + R2. There will be 1 futility interim analysis (IA) and 1 efficacy IA for WT population and 1 efficacy IA for MT population.

Stage 3 is a long-term follow-up of patients for assessment of response and overall survival. All patients will be followed for survival until 5 years post last patient enrolled in the study.

Eligibility criteria: 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 \[β-hCG\] 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.
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.

Primary outcomes:
measure: Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2)
timeFrame: Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 was selected at the end of Stage 1
measure: Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) population
timeFrame: Stage 2: Up to 72 months
measure: PFS in the Intent-to-treat mutant-type (ITT-MT) population
timeFrame: Stage 2: Up to 72 months
Secondary outcomes:
measure: Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax).
timeFrame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
measure: PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax)
timeFrame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
measure: 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)],
timeFrame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
measure: PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)]
timeFrame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
measure: The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit
timeFrame: Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle)
measure: Complete Response Rate (CRR) in ITT-WT population
timeFrame: Stage 2: Up to 96 months
measure: CRR in ITT-MT population
timeFrame: Stage 2: Up to 96 months
measure: CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status
timeFrame: Stage 2: Up to 96 months
measure: Objective Response Rate (ORR) in the ITT-WT population
timeFrame: Stage 2: Up to 96 months
measure: ORR in the ITT-MT population
timeFrame: Stage 2: Up to 96 months
measure: ORR in the R/R FL population regardless of mutation status
timeFrame: Stage 2: Up to 96 months
measure: Overall Survival (OS) in the ITT-WT population
timeFrame: Stage 2: Up to 96 months
measure: OS in the ITT-MT population
timeFrame: Stage 2: Up to 96 months
measure: OS in the R/R FL population regardless of mutation status
timeFrame: Stage 2: Up to 96 months
measure: PFS in the ITT-WT population, assessed by a blinded IRC
timeFrame: Stage 2: Up to 96 months
measure: PFS in the ITT-MT population, assessed by a blinded IRC
timeFrame: Stage 2: Up to 96 months
measure: PFS in the R/R FL population regardless of mutation status, assessed by a blinded IRC
timeFrame: Stage 2: Up to 96 months
measure: PFS in the R/R FL population regardless of mutation status, assessed by the Investigator
timeFrame: Stage 2: Up to 96 months
measure: Duration Of Response (DOR) in the ITT-WT population
timeFrame: Stage 2: Up to 96 months
measure: DOR in the ITT-MT population
timeFrame: Stage 2: Up to 96 months
measure: DOR in the R/R FL population regardless of mutation status
timeFrame: Stage 2: Up to 96 months
measure: Duration Of Complete Response (DOCR) in the ITT-WT population
timeFrame: Stage 2: Up to 96 months
measure: DOCR in the ITT-MT population
timeFrame: Stage 2: Up to 96 months
measure: DOCR in the R/R FL population regardless of mutation status
timeFrame: Stage 2: Up to 96 months
measure: Disease Control Rate (DCR) in the ITT-WT population
timeFrame: Stage 2: Up to 96 months
measure: DCR in the ITT-MT population
timeFrame: Stage 2: Up to 96 months
measure: DCR in the R/R FL population regardless of mutation status
timeFrame: Stage 2: Up to 96 months
measure: Population PK parameters of oral clearance (CL/F) of tazemetostat
timeFrame: Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
measure: Population PK parameters of oral volume of distribution (Vd/F) of tazemetostat.
timeFrame: Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
measure: Population PK parameters of first-order absorption rate constant (Ka) for tazemetostat.
timeFrame: Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle)
measure: Percentage of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 36 months
measure: Percentage of Participants with Clinically Significant Changes in Physical Examination
timeFrame: Up to 36 months
measure: Percentage of Participants with Clinically Significant Changes in Vital Signs
timeFrame: Up to 36 months
measure: Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings
timeFrame: Up to 72 months
measure: Performance status evaluated by Eastern Cooperation Oncology Group (ECOG)
timeFrame: Up to 72 months
measure: Duration of Study Drug Exposure
timeFrame: Up to 36 months
measure: Percentage of study drug taken by participants
timeFrame: Up to 36 months
measure: Quality of life questionnaires evaluation
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Southern Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates - Tuscon-Rusadill Road
state: Arizona
city: Cerritos
country: United States
facility: TOI - Clinical Research
state: California
city: Clovis
country: United States
facility: UCSF Fresno
state: California
city: La Jolla
country: United States
facility: UC San Diego Health Sciences
state: California
city: Santa Monica
country: United States
facility: UCLA Clinical Research Unit Hematology/Oncology
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers (RMCC) - Boulder
state: Colorado
city: Grand Junction
country: United States
facility: St. Mary's Hospital and Regional Medical Center - St. Mary's
state: Colorado
city: Greeley
country: United States
facility: SCL Health Lutheran Medical Center
state: Colorado
city: Fleming Island
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists & Research Institute (FCS) - Fort Myers Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Cancer Clinical Research Office
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Ocala
country: United States
facility: Florida Cancer Affiliates/Ocala Oncology - Clinic
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center, INC
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists - Panhandle
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute I
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists & Research Institute (FCS) - Atlantis
state: Florida
city: Honolulu
country: United States
facility: Kaiser Permanente Hawaii Moanalua Medical Center
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Sioux City
country: United States
facility: June E. Nylen Cancer Center
state: Iowa
city: Overland Park
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Chevy Chase
country: United States
facility: The office of Frederick P. Smith, MD, P.C.
state: Maryland
city: Newton
country: United States
facility: Mass General Cancer Center at Newton-Wellesley
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University Of Nebraska Medical Center
state: Nebraska
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: East Brunswick
country: United States
facility: Astera Cancer Center
state: New Jersey
city: Freehold
country: United States
facility: Regional Cancer Care Associates-Freehold
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical John Theurer Cancer Center
state: New Jersey
city: Howell
country: United States
facility: Regional Cancer Care Associates LLC - Howell
state: New Jersey
city: Little Silver
country: United States
facility: Regional Cancer Care Associates LLC - Little Silver
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Lake Success
country: United States
facility: Northwell Health/Monter Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Columbia U - Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nyack
country: United States
facility: Hematology Oncology Associates of Rockland, P.C.
state: New York
city: Asheville
country: United States
facility: Messino Cancer Center
state: North Carolina
city: Concord
country: United States
facility: Levine Cancer Institute - Concord
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth of the Carolinas
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care (OHC), Inc. - Kenwood Office
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center - Oncology
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Oncology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital Hematology & Cellular Therapy
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center - Cancer Institute
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Amarillo
country: United States
facility: Texas Oncology - Amarillo
state: Texas
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas Pediatric Hematology
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Millennium Physicians - Oncology
state: Texas
city: Plano
country: United States
facility: Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Center
state: Texas
city: Tyler
country: United States
facility: UT Health East Texas HOPE Cancer Center - Tyler
state: Texas
city: Tyler
country: United States
facility: USO Texas Oncology - Tyler
state: Texas
city: Weslaco
country: United States
facility: Texas Oncology- Weslaco
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists/ IHO Corp
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute; The University of Utah
state: Utah
city: Chesapeake
country: United States
facility: Peninsula Cancer Institute
state: Virginia
city: Gainesville
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia Inc.
state: Virginia
city: Spokane
country: United States
facility: MC Rockwood Cancer Bl Specialty Ctr - North
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital - North Star Lodge Cancer Center
state: Washington
city: Wheeling
country: United States
facility: Wheeling Hospital
state: West Virginia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health, University Hospital Geelong
state: Victoria
city: Nedlands
country: Australia
facility: Hollywood Private Hospital
state: Western Australia
city: Adelaide
country: Australia
facility: GenesisCare - St Andrew's
city: Frankston
country: Australia
facility: Peninsula Health - Frankston
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Southport
country: Australia
facility: Gold Coast University Hosptial
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne UCL Namur
state: Namur
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg
state: Vlaams Brabant
city: Toronto
country: Canada
facility: University Health Network Princess Margaret Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: Sir Mortimer B Davis/Jewish General Hospital
state: Quebec
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zhejiang
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Hangzhou
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jinlin
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Beijing
country: China
facility: Peking University Third Hospital
city: Hangzhou
country: China
facility: Tongji Hospital of Tongji Medical College of HUST
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
city: Shanghai
country: China
facility: Tongji Hospital of Tongji University
city: Sichuan
country: China
facility: Sichuan Provincial People's Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Pessac Cedex
country: France
facility: Centre Hospitalier Universitaire de Bordeaux-Hopital du Haut Leveque
state: Aquitaine
city: Brest
country: France
facility: CHRU Brest Hôp Morvan
state: Bretagne
city: Bordeaux
country: France
facility: Institut Bergonie
state: Gironde
city: Mulhouse
country: France
facility: Centre Hosp Mulh Hop Emile Muller
state: Haut-Rhin
city: Rouen
country: France
facility: Centre Henri Becquerel
state: Haute-Normandie
city: Limoges
country: France
facility: CHU de Limoges Dupuytren
state: Haute-Vienne
city: La Tronche
country: France
facility: CHU de Grenoble - Hopital Albe
state: Isere
city: Nantes
country: France
facility: CHU de Nantes - Hematologie
state: Loire-Atlantique
city: Lille
country: France
facility: CHRU de Lille Hop Claude Huriez
state: Nord
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
state: Sarthe
city: Angers
country: France
facility: Centre Hospitalier Universitaire D'Angers - Hématologie Clinique
city: Besancon
country: France
facility: CHRU de Besançon- Hopital Jean Minjoz
city: Caen
country: France
facility: CHU Caen
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand, site Estaing
city: Lens
country: France
facility: Centre Hospitalier Docteur Schaffner
city: Nantes
country: France
facility: L'Hôpital Privé Confluent
city: Nantes
country: France
facility: L'hôpital Privé du Concluent
city: Paris
country: France
facility: Hopital Saint Louis
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Périgueux
country: France
facility: Centre Hospitalier - Hôpital de jour d'Hématologie
city: Vandœuvre-lès-Nancy
country: France
facility: CHU de Nancy Brabois
city: Vannes
country: France
facility: Centre Hospitalier Bretagne Atlantique
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Créteil
country: France
facility: Hopital Henri Mondor - Hemopathies Lymphoides
state: Île-de-France
city: Schwäbisch Hall
country: Germany
facility: Diakoneo Diak Schwaebisch Hall gGmbH
state: Baden-Württemberg
city: München
country: Germany
facility: Klinikum Der Universität München AöR
state: Bayern
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universitat Muenche
state: Bayern
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
state: Hessen
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn AöR
state: Nordrhein-Westfalen
city: Moenchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Städt. Krankenhaus Kiel
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Vivantes Klinikum am Urban Hämatologie und Onkologie
city: Kiel
country: Germany
facility: University Medical Center Schleswig Holstein
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
state: Hajdú-Bihar
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Általános Orvostudományi Kar
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz Orszagos Hematologiai és Infektologiai Intezet
city: Napoli
country: Italy
facility: AOU Federico II
state: Campania
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori IRCCS
state: Forli-Cesena
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Catania
country: Italy
facility: PO Garibaldi-Nesima, ARNAS Garibaldi
city: Firenze
country: Italy
facility: AOU Careggi
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi, ASL Lecce
city: Milano
country: Italy
facility: IEO - Istituto Europeo di Oncologia, IRCCS
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
city: Milano
country: Italy
facility: Ospedale Niguarda, ASST Grande Ospedale Metropolitano Niguarda
city: Monza
country: Italy
facility: Ospedale San Gerardo, ASST di Monza
city: Pescara
country: Italy
facility: Ospedale Civile S.Spirito, PO di Pescara, AUSL Pescara
city: Rimini
country: Italy
facility: Ospedale Infermi di Rimini, AUSL Rimini, Distretto di Rimini, Presidio di Rimini, Santarcangelo di Romagna e Novafeltria
city: Roma
country: Italy
facility: Catholic University Of Sacred Heart
city: Roma
country: Italy
facility: PU Campus Bio-Medico di Roma
city: Roma
country: Italy
facility: Regina Elena, Istituto Nazionale dei Tumori , IFO, IRCCS
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino, Ospedale Umberto I di Torino
city: Treviso
country: Italy
facility: Ospedale S.Giacomo Apostolo, PO Castelfranco Veneto, AULSS 2 Marca Trevigiana
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI), Ospedale Maggiore
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
state: Seoul Teugbyeolsi [Seoul-T'ukp]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul Teugbyeolsi [Seoul-T'ukp
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi [Seoul-T'ukp
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
state: Mazowieckie
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
state: Wielkopolskie
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Kraków
country: Poland
facility: Pratia MCM Krakow
city: Słupsk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
city: Torun
country: Poland
facility: MICS Centrum Medyczne Torun
city: Warszawa
country: Poland
facility: MTZ Clinical Research powered by Pratia
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
state: Cataluny
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Madrid
country: Spain
facility: Hospital Univ. Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Pamplona
country: Spain
facility: C.H. de Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Nuestra Señora de Valme
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen De La Macarena
city: Hualien City
country: Taiwan
facility: Buddihist Tzu Chi Medical Foundation- Hualien Tzu Chi Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty - Hematology
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Istanbul
country: Turkey
facility: Medipol Bagcilar Mega Hospital
city: Samsun
country: Turkey
facility: Ondokuz Mayis University Medical Faculty - Hematology
city: Edinburgh
country: United Kingdom
facility: Western General Hospital - Haematology
state: Edinburgh, City Of
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust - Hammersmith Hospital
state: London City
city: London
country: United Kingdom
facility: St Bartholomew's Hospital Barts Health NHS Trust
state: London, City Of
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust - Clatterbridge Cancer Centre
city: Cornwell
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust - Royal Cornwall Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Middlesex
country: United Kingdom
facility: Northwick Park Hospital Middlesex, United Kindgom, HA1 3UJ
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: