Clinical Trials /

Combination Therapy With Entinostat and Pembrolizumab in Relapsed and Refractory Lymphomas

NCT03179930

Description:

The purpose of this study is to test any good and bad effects of the study drugs called Pembrolizumab and Entinostat when used in combination to treat lymphoma. This combination could shrink the lymphoma but it could also cause side effects. Researchers also hope to learn whether adding entinostat to pembrolizumab can be more effective for patients with lymphoma than either drug alone.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Combination Therapy With Entinostat and Pembrolizumab in Relapsed and Refractory Lymphomas
  • Official Title: A Phase II Study of Pembrolizumab and Entinostat in Patients With Relapsed and Refractory Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 17-073
  • NCT ID: NCT03179930

Conditions

  • Lymphoma
  • Relapsed
  • Refractory

Interventions

DrugSynonymsArms
EntinostatEntinostat and Pembrolizumab
PembrolizumabEntinostat and Pembrolizumab

Purpose

The purpose of this study is to test any good and bad effects of the study drugs called Pembrolizumab and Entinostat when used in combination to treat lymphoma. This combination could shrink the lymphoma but it could also cause side effects. Researchers also hope to learn whether adding entinostat to pembrolizumab can be more effective for patients with lymphoma than either drug alone.

Trial Arms

NameTypeDescriptionInterventions
Entinostat and PembrolizumabExperimentalpatients will be assigned to receive therapy with entinostat given by mouth once weekly and pembrolizumab given intravenously every 3 weeks
  • Entinostat
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patient is ≥ 18 years of age at the time of signing Informed Consent

          -  Patient has histologically confirmed diagnosis of classical Hodgkin lymphoma at
             enrolling institution.

          -  Hodgkin lymphoma patients must have received at least 2 prior regimens. Patients
             should have declined, or be ineligible for autologous transplant

          -  Prior HDAC inhibitor and/or anti-PD1, anti-PDL1, anti-PD-L2, anti-CD137 or
             anti-cytotoxic T- lymphocyte associated antigen 4 (CTLA-4) antibody allowed as long
             patient received clinical benefit from it. Patients can currently be on a checkpoint
             inhibitor or HDAC inhibitor, including one of the study drugs, at time of screening.

          -  Patient has at least one site of measurable disease (≥ 1.5 cm), which may be lymph
             node or extranodal lesion, which is seen on screening imaging studies within 28 days
             of start of study drug

          -  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

               -  Hemoglobin (Hgb) ≥ 9.0 g/dL

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 x ULN
                  (or

                  ≤3 x ULN if liver involved with disease

               -  Total serum bilirubin ≤ 1.5 x ULN ( ≤ 3 x ULN with direct bilirubin within normal
                  range in patients with documented hepatic involvement, well documented Gilbert‟s
                  Syndrome)

               -  International Normalized Ratio (INR) or Prothrombin

               -  Time (PT) ≤1.5×ULN unless patient is receiving anticoagulant therapy as long as
                  PT or PTT is within therapeutic range of intended use of anticoagulants

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5×ULN unless patient is receiving
                  anticoagulant therapy as long as PT or PTT is within therapeutic range of
                  intended use of anticoagulants

               -  Patients with GFR<45 ml/min. Patients with GFR 45-60 ml/min are eligible but will
                  undergo dose adjustments as specified in section 9.0.1

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          -  Female subjects of childbearing potential must be willing to use an adequate method of
             contraception. Subjects must adhere to the contraception requirement from the day of
             study medication initiation, (or 14 days prior to the initiation of study medication
             for oral contraception) throughout the entire study, and up 120 days after the last
             dose of trial therapy.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

          -  Male subjects of childbearing potential (Section 9.8.2) must agree to use an adequate
             method of contraception as outlined in Section 9.8.2- Subjects must adhere to the
             contraception requirement from the day of study medication initiation, (or 14 days
             prior to the initiation of study medication for oral contraception) throughout the
             entire study, and up 120 days after the last dose of trial therapy.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Exclusion Criteria:

          -  Diagnosed or treated for malignancy other than the indication under study except for

               -  Malignancy treated with curative intent and with no known active disease present
                  for at least 2 years before the first dose of study treatment

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated cervical carcinoma in situ without evidence of disease

          -  History of Human Immunodeficiency Virus (HIV)

          -  Active Hepatitis B or C infection

          -  History of active TB (Bacillus Tuberculosis)

          -  Concurrent enrollment in another therapeutic investigational clinical study or has
             participated in a study of an investigational agent and received study therapy or used
             an investigational device within 4 weeks of the first dose of study drug

          -  Known CNS lymphoma involvement

          -  Any uncontrolled active systemic infection or any life-threatening illness, medical
             condition, or organ system dysfunction which, in the investigator‟s opinion, could
             compromise the subject‟s safety, interfere with the absorption or metabolism of
             entinostat capsules, or put the study outcomes at undue risk.

          -  Any history of (non-infectious) pneumonitis that required steroids, evidence of
             interstitial lung disease or active, non- infectious pneumonitis

          -  Myocardial infarction or arterial thromboembolic events within 6 months prior to
             baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or
             IV disease, or a QTc interval > 470 msec.

          -  History of Torsades de pointes, ventricular tachycardia, or ventricular fibrillation
             within 6 months prior to screening

          -  Uncontrolled heart failure or hypertension or uncontrolled diabetes mellitus

          -  Any active autoimmune disease or a documented history of autoimmune disease
             (excluded/exception to the rule: subjects with vitiligo or resolved childhood
             asthma/atopy, type I diabetes mellitus, subjects with hypothyroidisms stable on
             hormone replacement, Sjorgen‟s syndrome, psoriasis not requiring systemic treatment,
             or conditions not expected to recur in the absence of an external trigger).

          -  Any syndrome that requires ongoing systemic treatment with either corticosteroids (>
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 7
             days of study drug administration. Of note: Inhaled or topical steroids, and adrenal
             replacement doses are permitted

          -  Women who are pregnant or breast feeding

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or has persistent and uncontrolled adverse events from most recent prior
             therapy.

          -  Has had an allogenic tissue/solid organ transplant

          -  Has had recent chemotherapy within 2 weeks prior to study day 1

          -  Has had recent small molecule therapy within 3 half-lives of agent prior to study day
             1

             °Participants must have recovered from all AEs due to previous therapies to </= Grade
             1 or baseline. Participants with </= Grade 2 neuropathy may be eligible

          -  Has the patient received radiotherapy (with the exclusion of radiation to one area
             [e.g. involved nodal sit] that does not interfere with response assessment in other
             sites) within 2 weeks prior to study day 1?

             °Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis

          -  Allergy to benzamide or inactive components of entinostat
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response using the 2014 Lugano Classification
Time Frame:2 years
Safety Issue:
Description:will be evaluated in this study using the 2014 Lugano Classification.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Entinostat
  • Pembrolizumab
  • 17-073

Last Updated

December 31, 2019