Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01897571




Registration number
NCT01897571
Ethics application status
Date submitted
21/06/2013
Date registered
12/07/2013
Date last updated
26/03/2024

Titles & IDs
Public title
Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL
Scientific title
An Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With Diffuse Large B Cell Lymphoma
Secondary ID [1] 0 0
2012-004083-21
Secondary ID [2] 0 0
E7438-G000-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Lymphomas (Phase 1) 0 0
Advanced Solid Tumors (Phase 1) 0 0
Diffuse Large B-cell Lymphoma (Phase 2) 0 0
Follicular Lymphoma (Phase 2) 0 0
Transformed Follicular Lymphoma 0 0
Primary Mediastinal Large B-Cell 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 - Prednisolone
Treatment: Drugs - Tazemetostat

Experimental: Phase 1 - Patients in the Phase 1 portion of the study.

Experimental: Phase 2 Group 1: Tazemetostat in R/R FL with Mutant EZH2 - Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.

Experimental: Phase 2 Group 2: Tazemetostat in R/R FL with Wild-Type EZH2 - Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.

Experimental: Phase 2 Group 3: Tazemetostat in R/R DLBCL - Patients with R/R DLBCL treated with tazemetostat as a single agent or tazemetostat in combination with prednisolone in Phase 2 of the study.


Treatment: Drugs: Tazemetostat
Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.

Treatment: Drugs: Prednisolone
Patients who received 40 mg/m\^2 prednisolone once daily on Days 1-5 and 15-19 of Cycles 1-4.

Treatment: Drugs: Tazemetostat
Patients who received 100 mg to 1600 mg of tazemetostat, BID, administered in continuous 28-day cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (RP2D) of Tazemetostat as a Single-Agent and in Combination With Prednisolone (Phase 1 Only)
Timepoint [1] 0 0
The first 28-day cycle of therapy
Primary outcome [2] 0 0
Objective Response Rate (ORR; Complete Response + Partial Response [CR + PR]) (Phase 2)
Timepoint [2] 0 0
Radiologic tumor assessments performed at baseline(within 28 days before start of study treatment)and every 8 weeks during Cycles 2 to 6,and then every 12 weeks thereafter until confirmed disease progression (PD)/death,a maximum of approximately 82 months
Secondary outcome [1] 0 0
Duration of Response for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)
Timepoint [1] 0 0
Radiologic tumor assessments performed at baseline (within 28 days before start of study treatment) and every 8 weeks during Cycles 2 to 6, and then every 12 weeks thereafter until confirmed PD/death, a maximum of approximately 82 months
Secondary outcome [2] 0 0
Progression Free Survival for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)
Timepoint [2] 0 0
Radiologic tumor assessments performed at baseline (within 28 days before start of study treatment) and every 8 weeks during Cycles 2 to 6, and then every 12 weeks thereafter until confirmed PD/death, a maximum of approximately 82 months

Eligibility
Key inclusion criteria
1. Phase 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Phase 2: ECOG performance status of 0 to 2.
2. Life expectancy of at least 3 months before starting tazemetostat.
3. Voluntary agreement to provide written informed consent and willing to adhere to all protocol requirements
4. Subjects with Hepatitis B or C are eligible on the condition that subjects have adequate liver function and are hepatitis B surface antigen negative and/or have undetectable hepatitis C virus (HCV) RNA.
5. Adequate renal and liver function
6. Phase 1: Males or females aged = 16 years at time of informed consent. Phase 2: Males or females aged = 18 years at the time of informed consent .
7. Females must not be lactating or pregnant at screening or baseline as documented by a negative pregnancy test All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dose). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to randomization, during Treatment Cycles, and for 6 months after the last final dose of study drug; any male partner must use a condom.
8. Male subjects must have had a successful vasectomy (with confirmed azoospermia) or they and their female partner must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception and use a condom throughout the study period and for 3 months after study drug discontinuation). Nonvasectomized male subjects must also agree to refrain from donating sperm from first dose of tazemetostat until 3 months following the last dose of tazemetostat
9. Phase 1 only: Histologically and/or cytologically confirmed advanced or metastatic solid tumor or B-cell lymphomas that have progressed after treatment with approved therapies or for which there are no standard therapies available.
10. Phase 2, Groups 1-6 only: Subjects must satisfy all of the following criteria:

1. Have histologically confirmed DLBCL (including primary mediastinal B-cell lymphoma), with relapsed or refractory disease following at least 2 lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] or equivalent) AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT) as defined by meeting at least 1 of the following criteria:

* Relapsed following, or refractory to, previous ASCT
* Did not achieve at least a partial response to a standard salvage regimen (eg, rituximab, ifosfamide, carboplatin, and etoposide phosphate [R-ICE] or rituximab, dexamethasone, cytarabine, and cisplatin [R-DHAP])
* Ineligible for intensification treatment due to age or significant comorbidity
* Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
* Refused intensification treatment and/or ASCT or
2. Have histologically confirmed Follicular Lymphoma (FL), all grades. Subjects may have relapsed/refractory disease following at least 2 standard prior systemic treatment regimens where at least 1 anti-CD20-based regimen was used. Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a systemic treatment regimen.
3. Have provided sufficient archival tumor tissue that has been successfully tested for EZH2 mutation status and cell of origin (DLBCL only)
4. Have measurable disease as defined by International Working Group-Non-Hodgkin's Lymphoma (IWG-NHL)
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
2. Subjects with leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
3. Has thrombocytopenia, neutropenia, or anemia of Grade =3 (per CTCAE 4.03 criteria) and any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
4. Has a prior history of T-cell lymphoblastic lymphoma(T-LBL) or T-cell lymphoblastic leukemia (T-ALL).
5. Subjects taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. Johns Wort) 6. Subjects unwilling to remove Seville oranges, grapefruit juice and grapefruit from their diet.
6. Any unstable or unresolved prior treatment-related (i.e. chemotherapy, immunotherapy, radiotherapy) toxicities at time of enrollment.
7. Major surgery within 4 weeks before the first dose of study drug. .
8. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of tazemetostat.
9. 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.
10. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
11. Active infection requiring systemic therapy.
12. Immunocompromised patients, including patients known to be infected with human immunodeficiency virus (HIV).
13. Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study.
14. Females who are pregnant or breastfeeding.
15. Phase 2 only: Subjects with noncutaneous malignancies other than B-cell lymphomas. Exception: Subjects with another malignancy who have been disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/06/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/11/2021
Sample size
Target
Accrual to date
Final
400
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Clayton
Recruitment hospital [2] 0 0
- Geelong
Recruitment hospital [3] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Geelong
Recruitment postcode(s) [3] 0 0
- Melbourne
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
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
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Montreal
Country [12] 0 0
Canada
State/province [12] 0 0
Toronto
Country [13] 0 0
France
State/province [13] 0 0
Bordeaux
Country [14] 0 0
France
State/province [14] 0 0
Caen
Country [15] 0 0
France
State/province [15] 0 0
Creteil
Country [16] 0 0
France
State/province [16] 0 0
Lille
Country [17] 0 0
France
State/province [17] 0 0
Lyon
Country [18] 0 0
France
State/province [18] 0 0
Marseille
Country [19] 0 0
France
State/province [19] 0 0
Montpellier
Country [20] 0 0
France
State/province [20] 0 0
Nantes
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Pierre Benite
Country [23] 0 0
France
State/province [23] 0 0
Rennes
Country [24] 0 0
France
State/province [24] 0 0
Rouen
Country [25] 0 0
France
State/province [25] 0 0
Villejuif Cedex
Country [26] 0 0
Germany
State/province [26] 0 0
Gottingen
Country [27] 0 0
Germany
State/province [27] 0 0
Muenster
Country [28] 0 0
Italy
State/province [28] 0 0
Bologna
Country [29] 0 0
Italy
State/province [29] 0 0
Napoli
Country [30] 0 0
Poland
State/province [30] 0 0
Krakow
Country [31] 0 0
Poland
State/province [31] 0 0
Lublin
Country [32] 0 0
Poland
State/province [32] 0 0
Poznan
Country [33] 0 0
Poland
State/province [33] 0 0
Warsaw
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taipei City
Country [35] 0 0
Ukraine
State/province [35] 0 0
Chernivtsi
Country [36] 0 0
Ukraine
State/province [36] 0 0
Dnipro
Country [37] 0 0
Ukraine
State/province [37] 0 0
Ivano-Frankivs'k
Country [38] 0 0
Ukraine
State/province [38] 0 0
Kharkiv
Country [39] 0 0
Ukraine
State/province [39] 0 0
Kyiv
Country [40] 0 0
Ukraine
State/province [40] 0 0
Mykolayiv
Country [41] 0 0
Ukraine
State/province [41] 0 0
Uzhgorod
Country [42] 0 0
Ukraine
State/province [42] 0 0
Zaporizhzhya
Country [43] 0 0
Ukraine
State/province [43] 0 0
Zhytomyr
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Glasgow
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Manchester
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Southampton

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01897571