Rollover Study for Tazemetostat

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Epizyme Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Aug 2016 → 26 Sep 2025

Decision date (initial)

2024-05-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Epizyme, Inc., US

External identifiers

EU CT number

2023-510553-41-00

EudraCT number

2015-004984-35

WHO UTN

U1111-1304-9435

ClinicalTrials.gov

NCT02875548

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacogenomic, Safety, Efficacy, Pharmacokinetic

Assess the long- term safety of tazemetostat

Secondary objectives 1

1. Determine the OS of subjects receiving tazemetostat

Conditions and MedDRA coding

Subjects will receive tazemetostat as dictated in their antecedent study.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1.Has demonstrated and continues to demonstrate clinical benefit from treatment with tazemetostat.
2. 2.Is currently receiving or is in survival follow-up having previously received tazemetostat as either monotherapy or in combination with other approved drug(s) or investigational agent(s) on an Epizymesponsored clinical trial or any other clinical trial being conducted with tazemetostat that is not sponsored by Epizyme (including but not limited to, investigator-initiated trials). For subjects on combination therapy, treatment with other therapeutic(s) must have been completed in the antecedent study or will be provided by a source other than Epizyme if combination therapeutics are continued in this study
3. 3.Has voluntarily provided signed written informed consent/assent and demonstrated willingness and ability to comply with all aspects of the protocol
4. 4.Has a life expectancy of >3 months
5. 5.Has adequate hematologic, (bone marrow [BM], and coagulation factors), renal, and hepatic function. Subject must remain eligible for continued treatment with tazemetostat according to the eligibility and treatment criteria from the antecedent study
6. 6. Female subjects of reproductive potential must have a negative urine/serum pregnancy test upon study entry. Female subjects who are of non-reproductive potential (ie, post- menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy) are exempt from pregnancy testing.
7. 7. Female subjects of reproductive potential who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (eg, condoms, cervical ring, sponge, etc) during the period of therapy and for 6 months after the last dose of tazemetostat. It is recommended that barrier methods be supplemented with the use of a spermicide.
8. 8. Male subjects must have had either a successful vasectomy AND remain abstinent/practice highly effective contraception and use a condom throughout the study period and for 3 months after tazemetostat discontinuation OR they and their female partner must meet the criteria above ie, not of childbearing potential.

Exclusion criteria 10

1. 1.Has had an interruption of tazemetostat dosing of >14 days from the antecedent clinical study to starting the rollover study
2. 2.Has an other malignancy other than the one for which they are receiving tazemetostat Exception: Subject who has been disease-free of a prior malignancy for 5 years, or subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible.
3. 3.Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE v5 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
4. 4.Has a prior history of T-LBL/T-ALL.
5. 5.Is unwilling to exclude grapefruit juice, Seville oranges, and grapefruit from the diet and all foods that contain those fruits from time of enrollment throughout their participation in the study.
6. 6.Is currently taking any prohibited medication(s) as described in Section 10.3
7. 7.Is unable to take oral medications, has malabsorption syndrome, or has any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of tazemetostat
8. 8.Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant bleeding diathesis or coagulopathy including known platelet function disorders, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmias or psychiatric illness/social situations that would limit compliance with study requirements
9. 8.Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant bleeding diathesis or coagulopathy including known platelet function disorders, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmias or psychiatric illness/social situations that would limit compliance with study requirements
10. 10. Has been permanently discontinued from tazemetostat therapy due to adverse event, intolerance or treatment failure.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Number of subjects with adverse events related to study drug, as a measure of safety and tolerability of tazemetostat
2. Number of subjects with adverse events, as a measure of safety and tolerability of tazemetostat
3. Extent of exposure to tazemetostat

Secondary endpoints 1

1. The OS of subjects receiving tazemetostat, defined as the interval of time between the date of the first dose of tazemetostat and the date of death due to any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Epizyme Inc.

Sponsor organisation

Epizyme Inc.

Address

1 Main Street

City

Cambridge

Postcode

02142-1531

Country

United States

Scientific contact point

Organisation

Epizyme Inc.

Contact name

Medical Development Director

Public contact point

Organisation

Epizyme Inc.

Contact name

Ipsen Clinical Study Enquiries

Third parties 5

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications