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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/15/2021.

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

Clinicaltrials.gov identifier NCT03939182

Recruitment Status Recruiting

First Posted May 6, 2019

Last update posted May 6, 2021

Study Description

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.

  • Condition or Disease:Diffuse Large B-cell Lymphoma
    Mantle Cell Lymphoma
  • Intervention/Treatment: Drug: Abexinostat
    Drug: Ibrutinib
  • Phase: Phase 1/Phase 2
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 40 participants
  • Intervention Model: Single Group Assignment
  • Intervention Model Description: 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.
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: Phase I Study of Abexinostat and Ibrutinib in Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma
  • Actual Study Start Date: May 2019
  • Estimated Primary Completion Date: May 2022
  • Estimated Study Completion Date: May 2022
Arms and interventions
Arm Intervention/treatment
Experimental: Abexinostat and Ibrutinib
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
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.

Drug: Ibrutinib
Ibrutinib will be given at the FDA-approved dose for mantle cell lymphoma (MCL) of 560 mg orally daily for 28 day cycle.
Outcome Measures
  • Primary Outcome Measures: 1. the MTD of abexinostat when combined with ibrutinib [ Time Frame: 1 year ]
    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.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

- 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

- Hemoglobin (Hgb) ≥ 9.0 g/dL

°For patients with documented bone marrow involvement of underlying MCL or DLBCL at
time of study enrollment, Hgb must be ≥ 8.0 g/dL

- International Normalized Ratio (INR) ≤ 1.5

- Creatinine clearance > 25 mL/min as determined by the Cockcroft-Gault equation or a
24-hour urine collection

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ ULN (or ≤3 x ULN
if liver involved with disease Total serum bilirubin ≤ 1.5 ULN unless bilirubin rise
is due to Gilbert"s syndrome or of non-hepatic origin

- Normal serum potassium level with or without supplementation.

- Left Ventricular Ejection Fraction (LVEF) ≥ 50%

- Women of childbearing potential and men who are sexually active must be practicing a
highly effective method of birth control during and after the study consistent with
local regulations regarding the use of birth control methods for subjects
participating in clinical trial. For females, these restrictions apply for 30 days
month after the last dose of study drug. For males, these restrictions apply for 120
days after the last dose of study drug. Refer to section 9.7 "Reproductive toxicity"
for additional details

- Women of childbearing potential must have a negative urine pregnancy test at Screening
and within 7 days of treatment initiation

- Men must agree to not donate sperm during and 12 months after the study. Women should
not donate ova/ooctyes for the purposes of

- Patient is able to swallow and retain oral medications

Exclusion Criteria:

- 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)
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.

- Hepatisis B surface antigen and core antibody testing are required at screening.
If Hepatisis B surface antigen is positive then HBV PCR is required and if
positive, then patient will be excluded.

- Hepatisis C antibody testing is required at screening. If positive, Hepatisis C
PCR is required and if positive, pHepatisis C PCR is required and if positive,
then patient will be excluded.

- Patient has hepatic failure (Child-Pugh Class C)

- Patient is currently receiving increasing or chronic treatment (> 10 days) with
corticosteroids or another immunosuppressive agent. Patients requiring chronic therapy
with steroids may take no more than 10mg daily of prednisone or equivalent.

- Patient requires chronic treatment with a strong cytochrome P450 (CYP) 3A4 inhibitors,
and inducers, or drugs known to induce Torsades de Pointes and the treatment cannot be
discontinued or switched to a different medication prior to starting study drug
(Appendix 1 and 3).

- Patients with known bleeding diathesis (e.g. von Willebrand "s disease) or hemophilia

- Patient is currently receiving warfarin or other Vitamin K antagonist. Therapy with
heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed. Refer to
Section 9.5 for Concomitant medication

- Vaccinated with live, attenuated vaccines within 4 weeks of randomization

- Patients with any life-threatening illness, medical condition or organ system
dysfunction that in the opinion of the investigator could compromise the subject"s
safety, interfere with absorption of metabolism of study drugs or put the study
outcomes at undue risk.

- Women who are pregnant or breastfeeding.

Contacts and Locations
Contacts

Contact: Gottfried von Keudell, MD 212-639-3748 vonkeudg@mskcc.org

Contact: Maria Palomba, MD 212-639-7186

Locations

United States, New Jersey
Memoral Sloan Kettering Basking Ridge
Basking Ridge

United States, New Jersey
Memoral Sloan Kettering Monmouth
Middletown

United States, New York
Memorial Sloan Kettering Commack
Commack

United States, New York
Memorial Sloan Kettering Westchester
Harrison

United States, New York
Memorial Sloan Kettering Cancer Center
New York

United States, New York
Memorial Sloan Kettering Rockville Centre
Rockville Centre

United States, Pennsylvania
Lehigh Valley Health Network
Allentown

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Janssen Scientific Affairs, LLC

Xynomic Pharmaceuticals, Inc.

Investigators

Principal Investigator: Gottfried von Keudell, MD Memorial Sloan Kettering Cancer Center

More Information
  • Responsible Party: Memorial Sloan Kettering Cancer Center
  • ClinicalTrials.gov Identifier: NCT03939182 History of Changes
  • Other Study ID Numbers: 19-080
  • First Posted: May 6, 2019 Key Record Dates
  • Last Update Posted: May 6, 2021
  • Last Verified: May 2021
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
  • Supporting Materials: Statistical Analysis Plan (SAP), Informed Consent Form (ICF)
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Memorial Sloan Kettering Cancer Center: Abexinostat
    Ibrutinib
    19-080
  • Additional relevant MeSH terms: Lymphoma
    Lymphoma, B-Cell
    Lymphoma, Mantle-Cell
    Lymphoma, Large B-Cell, Diffuse