Intervention: Mocetinostat
Trial phase: Phase 1 | Phase 2
SMILES: Nc1ccccc1NC(=O)c1ccc(CNc2nccc(-c3cccnc3)n2)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 7
Group description: Participants who harbor mutations for CREBBP and/or EP300 will be started on mocetinostat. The dose was escalated in cycle 2 to 90mg in the absence of DLTs.
Eligibility criteria:
Inclusion Criteria:

Patient has provided a signed study Informed Consent Form prior to performance of any study related procedurePatient is ≥ 18 years of age
Patient has histologically confirmed diagnosis of diffuse large B cell lymphoma or follicular lymphoma harboring mutations in CREBBP or EP300 with relapsed or refractory disease
Patients with diffuse large B cell lymphoma must have received at least two prior therapies and have received, declined or be ineligible for autologous or allogeneic stem cell transplant.
Patients with follicular lymphoma must have received at least two prior therapies.
Patients with either diffuse large B cell lymphoma or follicular lymphoma will be allowed to enroll after receiving only 1 prior therapy if they are felt to not be a candidate for further systemic chemotherapy.
Patient has at least one measurable lesion (≥ 2 cm) according to Cheson criteria [45]. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 - Patient has adequate bone marrow and organ function by:

Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L

Platelets ≥ 75 x 10^9/L (no platelet transfusion within past 14 days)
Hemoglobin (Hgb) ≥ 9.0 g/dL (no RBC transfusion within past 14 days)
International Normalized Ratio (INR) ≤ 1.5
Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x ULN, or ≤ 5.0 x ULN for patients with documented hepatic involvement
Serum bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for patients with Gilbert Syndrome or documented hepatic involvement.
Patients must have fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual grade 1 toxicity, e.g. grade 1 peripheral neuropathy, and residual alopecia are allowed)

Exclusion Criteria:

Patient has received previous treatment with HDAC inhibitors
Patient has evidence of graft versus host disease (GVHD)
Patient has active or history of central nervous system (CNS) disease
Patient has impaired cardiac function including any of the following:
Presence or history of pericardial effusion (definitions are provided in and/or pericarditis.
Acute myocardial infarction, symptomatic angina pectoris ≤ 6 months prior to starting study drug
Presence of congestive heart failure ≥ NYHA class 3
QTc > 480 ms on a screening ECG
Screening LVEF < 45% by echocardiography or MUGA
Uncontrolled cardiac arrhythmia including uncontrolled atrial fibrillation/atrial flutter/sinus tachycardia, complete left bundle branch block, congenital long QT syndrome
Presence of permanent cardiac pacemaker
Other clinically significant heart disease
Subject is taking warfarin at start of treatment or within 6 months prior to start of study treatment.
Patient has a concurrent malignancy or has a malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or nonmelanomatous skin cancer)
Patient is concurrently using other approved or investigational antineoplastic agent
Patient has received chemotherapy, targeted anticancer therapy, pelvic and/or para-aortic radiotherapy or has had major surgery ≤ 4 weeks (6 weeks for nitrosourea, monoclonal antibodies or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of mocetinostat (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
Patient is currently receiving increasing or chronic treatment (> 10 days) with corticosteroids or another immunosuppressive agent. The following uses of corticosteroids are permitted: single dose, topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
Patient has a history of non-compliance to medical regimen or inability to grant consent.
Concomitant medications causing prolonged QT which cannot be discontinued or changed to a different medication prior to initiating study
Patient is currently being treated with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Patients must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the start of treatment.

Note: the oral anti-diabetic drugs troglitazone and pioglitazone are CYP3A inducers.

Patient has a known history of HIV (testing not mandatory), active Hepatitis B or C infection.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum hCG laboratory test (> 5 mIU/mL)
Women of child bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter