Study of Mocetinostat in Selected Patients With Mutations of Acetyltransferase Genes in Relapsed and Refractory Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

NCT02282358 | Terminated Phase 1 Results

• 1 other identifier: 14-106
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn if the study drug mocetinostat can slow the progression of cancer in people who have a mutation in CREBBP or EP300 in the genetic makeup of their cancer. The potential side effects of mocetinostat will also be studied.

Conditions

Lymphoma; Relapsed and Refractory; Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

Keywords

Mocetinostat; 14-106

Outcome Measures

Primary Outcomes (1)

• Efficacy as Defined by Overall Response

  as defined by overall response rate of Mocetinostat at one year in patients with relapsed/refractory DLBCL and FL who have inactivating mutations of acetyltransferase genes. Response will be measured according to the 2007 revised Cheson criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=50% decrease in sum of the product of the diameters (SPD) of up to 6 dominant lesions identified at baseline; Overall Response (OR) = CR + PR.

  1 year

Secondary Outcomes (3)

• Event Free Survival

  up to 17.8 months

• Median Progression Free Survival/PFS

  up to 17.8 months

• Number of Participants Evaluated for Toxicity According to the (NCI CTCAE) Version 4.0.

  2 years

Study Arms (1)

Mocetinostat

EXPERIMENTAL

Patients who harbor mutations for CREBBP and/or EP300 will be started on mocetinostat 70 mg orally three times per week on a 28 day schedule in cycle 1. The dose will be escalated in cycle 2 to 90 mg orally three times per week on a 28 day schedule if there are no grade 3 or higher drug related toxicities. Therapy will continue until disease progression, intolerable toxicities or death.

Drug: Mocetinostat

Interventions

Mocetinostat DRUG

Mocetinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• MethylGene Inc.: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma; Recurrence; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

mocetinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Results Point of Contact

• Title: Dr. Andrew Zelenetz, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

zeleneta@mskcc.org

646-608-3728

Study Officials

• Andrew Zelenetz, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: November 4, 2014
• Study Start: October 1, 2014
• Primary Completion: May 26, 2023
• Study Completion: May 26, 2023
• Last Updated: March 8, 2024
• Results First Posted: March 8, 2024

Record last verified: 2023-05

Locations

US (1)