Study of tazemetostat in newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) patients treated by R-CHOP

Phase 1

• Conditions: newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL); MedDRA version: 19.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001499-31-FR
• Lead Sponsor: YSARC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-10-19
• Last Update Posted: 24 October 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 133

Inclusion Criteria

1. Patients with an untreated DLBCL de novo or transformed from indolent lymphoma (CD 20 positive) with aaIPI = 2
2. Age between 60 and 80 years included
3. ECOG performance status of 0, 1 or 2 (0 or 1 only for phase Ib)
4. Signed informed consent
5. Life expectancy of = 90 days (3 months) before starting tazemetostat
6. Adequate renal function as calculated by a creatinine clearance > 40 mL/min by local institutional formula
7. Adequate bone marrow function as defined as:
- ANC = 1500/mm3 (= 1.5 X 109/L)
- Platelets = 75,000/mm3 (= 75 X 109/L) without platelet transfusion dependency during the last 7 days
- Hemoglobin = 9 g/dL (may receive transfusion)
8. Adequate liver function as defined as:
- Total bilirubin = 1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert’s syndrome
- Alkaline phosphatase (in absence of bone disease), alanine aminotransferase (ALT) and asparatate aminotransferase (AST) = 3 X ULN (or = 5 X ULN if there is lymphoma involvement of the liver)
- Patients with prior Hepatitis B and C are eligible if for Hepatitis B detection, surface antigen is negative and/or HBV DNA is undetectable, and for Hepatitis C detection, HCV RNA is undetectable.
9. Left ventricular ejection fraction (LVEF) > 50% of echocardiography or multiple gated acquisition (MUGA) scan
10. Adequate tissue for central retrospective testing of EZH2 mutation status and cell of origin (15 slides of tumor biopsy must be available at screening)
11. Males with partners of childbearing potential must agree to use reliable forms of contraception

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 33
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Symptomatic central nervous system or meningeal involvement
2. Contraindication to any drug contained in the chemotherapy regimen
3. Prior treatment with tazemetostat or other inhibitor of EZH2
4. Patients who are undergoing active treatment for another malignancy, exceptions include: A patient who has been disease free for 2 years, or a patient with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible
5. Patients taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John’s wort) or known substrates of CYP2C8.
6. Patients unwilling to exclude Seville oranges, grapefruit juice and/or grapefruit from diet
7. Major surgery within 4 weeks before first dose of study drug (minor procedures including transcutaneous biopsy, central line placement are permitted within 2 weeks of enrollment)
8. Inability to take oral medication or malabsorption syndrome or any other uncontrolled gastrointestinal condition that would impare ability to take tazemetostat
9. Significant cardiovascular impairment: congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of first dose of tazemetostat or ventricular arrhythmia
10. Prolonged QTcF >480 msec
11. Active uncontrolled infection requiring systemic therapy
12. Congenital immunodeficiency or known HIV (human immunodeficiency virus infection)
13. Any other major illness that in the investigator’s judgement, will substantially increase the risk associated with the patient’s participation in the study
14. Patients who have undergone a solid organ transplant
15. Previous treatment for B cell lymphoma, except low dose radiotherapy for follicular lymphoma and glucocorticoids (no more than 14 days before inclusion, 1 mg/kg/day max)

Study & Design

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