Study of tazemetostat or placebo in combination with lenalidomide plus rituximab in subjects with relapsed/refractory follicular lymphoma

Phase 1

• Conditions: Relapsed/refractory follicular lymphoma; MedDRA version: 24.0Level: HLTClassification code 10016903Term: Follicle centre lymphomas, follicular grade I, II, IIISystem Organ Class: 10016903 - Follicle centre lymphomas, follicular grade I, II, III; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2019-003333-42-HU
• Lead Sponsor: Epizyme, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-10
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 518

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 (=20 years for Taiwan) at the time of providing voluntary written informed consent.
3. Life expectancy =3 months before enrollment.
4. Subjects with a history of 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. 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 Criteria #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. For subjects who have experienced any clinically significant toxicity related to a prior anticancer treatment (ie, chemotherapy, immunotherapy, and/or radiotherapy):
a. At the time the subject provides voluntary written informed consent, all toxicities have either resolved to Grade 1 per National Cancer Institute CTCAE Version 5.0 OR are clinically stable and no longer clinically significant.
9.Time between prior anticancer therapy and first dose of tazemetostat as follows:
a. Cytotoxic chemotherapy - At least 21 days.
b. Noncytotoxic chemotherapy (eg, small molecule inhibitor) - At least 14 days.
c. Nitrosoureas - At least 6 weeks.
d. Monoclonal and/or bispecific antibodies or CAR T - At least 28 days.
e. Radiotherapy -At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation.
10. Adequate renal function defined as calculated creatinine clearance =40 mL/minute per the Cockcroft and Gault formula.
11. Adequate bone marrow function
12. Adequate liver function
13. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 317
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 201

Exclusion Criteria

1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
2. Prior exposure to lenalidomide.
3. Grade 3b, mixed histology, or FL that has histologically transformed to 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).
5. Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL).
6. Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases.
7. 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.
8. 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.
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. Prolongation of corrected QT interval using Fridericia's formula (QTcF) to =480 msec at screening or history of long QT syndrome.
11. Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat.
a. whereas subjects greater than 3 months since deep vein thrombosis/pulmonary embolism are eligible but recommended to receive prophylaxis.
12. Have an active infection requiring systemic therapy.
13. Known hypersensitivity to any component of tazemetostat or lenalidomide; known severe hypersensitivity to any component of rituximab requiring hospitalization or resuscitation.
14. Inability to be treated with a Pneumocystis prophylaxis medication.
15. Active viral infection with or seropositive for hepatitis B virus (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 antiHBc 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.
16. Active viral infection with hepatitis C virus (as measured by positive HCV antibody and detectable viral RNA), human immunodeficiency virus (HIV), AND/OR human T-cell lymphotropic virus 1 (as measured by positive HTLV-1 antibody).
NOTE: Subjects with a history of hepatitis C infection (HCV antibody reactive) who have normal ALT and undetectable HCV RNA are eligible.
17. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
18. Female subjects who are pregnant or lactating/breastfeeding.
19. Subjects who have undergone a solid organ transplant.
20. Subjects with malignancies other than FL. a. Exception: Subjects with another malignancy who have been disease-free for 5 years, or subjects with a history o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified