Clinical Trials /

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

NCT03939182

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Mantle Cell Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abexinostat and Ibrutinib in Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma
  • Official Title: Phase I Study of Abexinostat and Ibrutinib in Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 19-080
  • NCT ID: NCT03939182

Conditions

  • Diffuse Large B-cell Lymphoma
  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
AbexinostatAbexinostat and Ibrutinib
IbrutinibAbexinostat and Ibrutinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Abexinostat and IbrutinibExperimentalThe 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.
  • Abexinostat
  • Ibrutinib

Eligibility 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 (≥ 2 cm) according to Lugano Classification

          -  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 ≥50 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. Men must agree to not donate sperm during and after
             the study. 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.

          -  Women of childbearing potential must have a negative serum (beta-human chorionic
             gonadotropin [β-hCG]) or urine pregnancy test at Screening.

          -  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) <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.

          -  Patient has acute viral hepatitis (typically defined by elevated AST/ALT), or a
             history of chronic or active HBV or HCV infection. HBV infection is defined as having
             HBsAg and/or HBcAb positive test with concurrent detectable HBV DNA levels. HCV
             infection is defined as detectable HCV RNA levels.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:the MTD of abexinostat when combined with ibrutinib
Time Frame:1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Abexinostat
  • Ibrutinib
  • 19-080

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