Abexinostat and Ibrutinib in Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma

NCT03939182 | Completed Phase 1 FDA Drug

• 1 other identifier: 19-080
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety of abexinostat at different doses to find out if it can work with ibrutinib to stop the cancer from growing.

Conditions

Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma

Keywords

Abexinostat; Ibrutinib; 19-080

Outcome Measures

Primary Outcomes (1)

• the MTD of abexinostat when combined with ibrutinib

  a standard 3+3 dose escalation scheme will be used. For any given dose an initial cohort of 3 patients will be treated at that dose. The dose level will be escalated if none of the 3 patients exhibits any DLT.

  1 year

Study Arms (1)

Abexinostat and Ibrutinib

EXPERIMENTAL

The investigational agents to be used in this study are ibrutinib and abexinostat. Ibrutinib will be administered once daily on a 28-day cycle. Abexinostat will be administered orally twice daily (approximately 4-6 hours apart) for 7 days a week given every other week on a 28-day cycle.

Drug: Abexinostat; Drug: Ibrutinib

Interventions

Abexinostat DRUG

Two doses of the abexinostat will be tested: 30 mg/m2 and 45 mg/m2 orally twice daily, 7 days/week given every other week during a 28-day cycle.

Abexinostat and Ibrutinib

Ibrutinib DRUG

Ibrutinib will be given at the FDA-approved dose for mantle cell lymphoma (MCL) of 560 mg orally daily for 28 day cycle.

Abexinostat and Ibrutinib

Eligibility Criteria

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

You may qualify if:

• Patient is ≥ 18 years of age at the time of signing Informed Consent
• Patient is able and willing to adhere to the study visit schedule and other protocol requirements
• Patient has histologically confirmed diagnosis of R/R mantle cell lymphoma or diffuse large B cell lymphoma
• Diffuse large B cell lymphoma patients must have received at least 1 prior regimen and received, declined, or is ineligible for autologous or allogeneic stem cell transplant.
• Diffuse large B cell lymphoma patients must have non-germinal center subtype disease applying the Hans classification algorithm using immunohistochemistry markers CD10, BCL6, and MUM1 (8).
• Mantle cell lymphoma patients must have received at least 1 line of therapy
• Allogeneic stem cell transplant recipients be greater than 6 months post transplant, not on immunosuppression for prevention of graft versus host disease for \>3 months and without active graft versus host disease
• Autologous stem cell transplant recipients must have adequate bone marrow recovery and are transfusion independent
• Patients with transformed DLBCL from an antecedent or simultaneous indolent B-cell Non-Hodgkin lymphoma are permitted.
• Patient has at least one measurable lesion (≥ 1.5 cm) according to RECIL
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patient has adequate bone marrow and organ function by:
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L independent of growth factor support
• Platelets ≥100 x 10\^9/L independent of transfusion
• °For patients with documented bone marrow involvement of underlying MCL or DLBCL at time of study enrollment, platelets must be ≥75 x 10\^9/L independent of transfusion

You may not qualify if:

• Patients previously treated with ibrutinib or HDAC inhibitor
• Patient has a history of non-compliance to medical regimen or inability to grant consent
• Patient is concurrently using other approved or investigational antineoplastic agent
• Patient has not recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
• Patient has had major surgery or a wound that has not fully healed within 4 weeks of starting study drugs.
• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study
• Patient has evidence of active graft versus host disease (GVHD)
• Patient has active central nervous system (CNS) disease or meningeal involvement.
• Patient has history of stroke or intracranial hemorrhage ≤ 6 months from starting study drugs.
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Patient has clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO), unstable angina pectoris, symptomatic pericarditis, QTcF \> 480 msec on the screening ECG (using the QTcF formula), or history of congenital long QT syndrome.
• Patient has a concurrent active malignancy.
• Malignancies treated with a curative intent with an expected life expectancy ≥ 5 years or a non-competing life expectancy risk are eligible (i.e. adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, early stage breast cancer, treated prostate cancer or any other cancer from which the patient has been disease free for ≥ 3 years).
• Patient with known history of human immunodeficiency virus (HIV), or any uncontrolled active systemic infection.
• Patients with acute viral hepatitis or a history of chronic or active HBV or HCV infection.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Janssen Scientific Affairs, LLC: collaborator
• Xynomic Pharmaceuticals, Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell

Interventions

abexinostat; ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Gilles Salles, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a phase I with dose expansion, open label single institution trial. The first stage is a standard 3+3 dose escalation trial. In the second stage, the dose expansion cohort will accrue patients at the MTD abexinostat and ibrutinib previously determined.

Study Record Dates

• First Submitted: May 3, 2019
• First Posted: May 6, 2019
• Study Start: May 29, 2019
• Primary Completion: April 22, 2025
• Study Completion: April 22, 2025
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF

Locations

US (7)