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Pembrolizumab and Entinostat in Treating Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

Trial Status: Active

This phase II trial studies how well pembrolizumab and entinostat work in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and entinostat may work better in treating patients with classical Hodgkin lymphoma.

Inclusion Criteria

  • Patient has histologically confirmed diagnosis of classical Hodgkin lymphoma at enrolling institution
  • Hodgkin lymphoma patients must have received at least 2 prior regimens; patient should have declined or be ineligible for autologous transplant
  • Prior histone deacetylase (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 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
  • 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 upper limit of normal (ULN) (or =< 3 x ULN if liver involved with disease)
  • Total serum bilirubin or plasma 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 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Patients with glomerular filtration rate (GFR) > 45 ml/min. Patients with GFR 45-59 ml/min are eligible but will undergo dose adjustments
  • 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 to 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 must agree to use an adequate method of contraception; subjects must adhere to the contraception requirement from the first 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 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 central nervous system (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 corrected QT (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, Sjogren'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
  • Women who are 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 adverse event (AEs) due to previous therapies to =< grade 1 or baseline; participants with =< grade 2 neuropathy may be eligible
  • Has received radiotherapy (with the exclusion of radiation to one area [e.g. involved nodal site] 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

Illinois

Chicago
Northwestern University
Status: ACTIVE
Contact: Barbara Pro

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: ACTIVE
Contact: Gottfried von Keudell
Phone: 646-608-3704
Middletown
Memorial Sloan Kettering Monmouth
Status: ACTIVE
Contact: Gottfried von Keudell
Phone: 646-608-3704
Montvale
Memorial Sloan Kettering Bergen
Status: ACTIVE
Contact: Gottfried von Keudell
Phone: 646-608-3704

New York

Commack
Memorial Sloan Kettering Commack
Status: ACTIVE
Contact: Gottfried von Keudell
Phone: 646-608-3704
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Gottfried von Keudell
Phone: 646-608-3704
Uniondale
Memorial Sloan Kettering Nassau
Status: ACTIVE
Contact: Gottfried von Keudell
Phone: 646-608-3704
West Harrison
Memorial Sloan Kettering Westchester
Status: ACTIVE
Contact: Gottfried von Keudell
Phone: 646-608-3704

PRIMARY OBJECTIVE:

I. Determine the 12 month progression-free survival rate of entinostat when administered in combination with pembrolizumab in patients with relapsed and refractory Hodgkin and follicular lymphomas.

SECONDARY OBJECTIVE:

I. Determine the disease control rate, overall response rate, complete response rate, progression-free survival, duration of response, safety, and tolerability of entinostat and pembrolizumab.

EXPLORATORY OBJECTIVE:

I. Determine whether pre-treatment tumor expression of B2M, MHC-I, MHC-II, PD-L1, or PD-L2, clone-specific alternations in T-cell or lymphoma cell gene expression, or serum cytokine levels at baseline or in response to therapy predicts treatment response.

OUTLINE:

Patients receive entinostat orally (PO) on days 1, 8, and 15 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 cycles (not to exceed 24 months) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients will be followed up at 30 and 90 days and every 4 months thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Gottfried von Keudell

  • Primary ID 17-073
  • Secondary IDs NCI-2017-01091
  • Clinicaltrials.gov ID NCT03179930