Combination Therapy With Entinostat and Pembrolizumab in Relapsed and Refractory Lymphomas

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03179930

Collaborator

Merck Sharp & Dohme LLC (Industry), Syndax Pharmaceuticals (Industry)

Enrollment

Locations

Arm

71.8

Anticipated Duration (Months)

5.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Relapsed Refractory	Drug: Entinostat Drug: Pembrolizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a protocol comprised of a multicenter phase II study in FL and HLThis is a protocol comprised of a multicenter phase II study in FL and HL

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Pembrolizumab and Entinostat in Patients With Relapsed and Refractory Lymphomas

Actual Study Start Date :

Jun 7, 2017

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Entinostat and Pembrolizumab patients will be assigned to receive therapy with entinostat given by mouth once weekly and pembrolizumab given intravenously every 3 weeks	Drug: Entinostat All patients will receive entinostat 5-7 mg PO as per the dosing regimen at the on D1, D8, and D15 Drug: Pembrolizumab pembrolizumab 200 mg IV on D1

Arm

Intervention/Treatment

Experimental: Entinostat and Pembrolizumab

patients will be assigned to receive therapy with entinostat given by mouth once weekly and pembrolizumab given intravenously every 3 weeks

Drug: Entinostat

All patients will receive entinostat 5-7 mg PO as per the dosing regimen at the on D1, D8, and D15

Drug: Pembrolizumab

pembrolizumab 200 mg IV on D1

Outcome Measures

Primary Outcome Measures

Response using the 2014 Lugano Classification [2 years]
will be evaluated in this study using the 2014 Lugano Classification.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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×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 45-59 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 or live-attenuated vaccine within 30 days of planned start of study therapy. Administration of killed vaccines is allowed. 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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University (Data Collection Only)	Evanston	Illinois	United States	60208
2	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
3	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
4	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
5	Roswell Park Cancer Institute (Data Collection Only)	Buffalo	New York	United States	14263-0001
6	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
7	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
8	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
9	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553