A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma

Subjects must meet all of the eligibility criteria to be enrolled on this study.

1. Subjects ≥18 years of age at the time the ICF is signed.

2. Have histologically confirmed FL, grades 1-3A

3. Must have been previously treated with at least 1 prior systemic therapy followed by relapsed, refractory or progressive disease.

a. Systemic therapy includes: i. Anti-CD20 monoclonal antibody in combination with chemotherapy ii. Anti-CD20 monoclonal antibody monotherapy iii. Anti-CD20 monoclonal antibody in combination with lenalidomide iv. Anti-CD20 monoclonal antibody plus investigational agent on protocol

4. Requiring systemic therapy as assessed by investigator based on tumor size, location, and/or GELF criteria.

5. Bi-dimensionally measurable disease, with at least one mass lesion ≥ 2 cm in longest diameter by CT, PET/CT, and/or MRI which was not previously irradiated.

6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

7. Adequate renal function defined as calculated creatinine clearance per the Cockcroft and Gault formula

* In phase 1, creatinine clearance must be \>60 mL/minute

* In Phase 2, creatinine clearance must be ≥30 mL/minute.

8. Adequate bone marrow function:

1. Absolute neutrophil count (ANC) ≥1,000/mm3 (≥1.0 × 109/L) if no lymphoma infiltration of bone marrow OR ANC ≥750/mm3 (≥0.75 × 109/L) with bone marrow infiltration, without growth factor support (filgrastim or pegfilgrastim) for at least 14 days.

2. Platelet ≥75,000/mm3 (≥75 × 109/L). Evaluated at least 7 days after platelet transfusion.

3. Hemoglobin \> 8.0 g/dL. Evaluated at least 7 days after RBC transfusion.

9. Adequate liver function:

1. Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome (eg, a gene mutation in UGT1A1), who can have total bilirubin \<3.0 mg/dL.

2. ALT and AST ≤3 × ULN.

10. International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless on warfarin, then INR ≤3.0).

11. If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at Screening and must be willing to use 1 highly effective method and 1 additional effective birth control method upon enrollment, during the Treatment Period, and for 3 months, following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose of study drug or confirmed by follicle stimulating hormone (FSH) test \>40 mIU/mL and estradiol \< 40 pg/mL (\<140 pmol/L).

12. If the subject is a male, the subject must be surgically sterile or willing to use a highly effective birth control upon enrollment, during the treatment period, and for 3 months following the last dose of study drug. Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and for at least 3 months after the final study drug administration

13. Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 3 months after the final study drug administration. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.

14. All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.

15. Able and willing to provide written informed consent and to comply with the study protocol

A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma

What this study is about

A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma

What this study is about