Safety & Efficacy Study of Combination of Pembrolizumab and Lenalidomide, in Patients With Relapsed Non-Hodgkin and Hodgkin Lymphoma

Study Overview
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Brief Summary
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This trial is to assess the safety & efficacy of the Combination of Pembrolizumab and Lenalidomide in the management of patients with Relapsed Hodgkin Lymphoma.

Detailed Description
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There is an emerging clinical data to confirm that Programmed death-1 (PD-1)blockade is safe and viable in lymphoma. The investigators hypothesize that the novel immune platform of pembrolizumab and lenalidomide, will be safe and well tolerated in patients with Relapsed Refractory (RR) Hodgkin Lymphoma (HL) and non-Hodgkin lymphoma (NHL) and that this combination will result in a complete response (CR) rate of 50% in patients with RR HL.

Official Title
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A Phase I/II Study of the Combination of Pembrolizumab and Lenalidomide, in Patients With Relapsed Non-Hodgkin and Hodgkin Lymphoma

Conditions
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Relapsed Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma

Intervention / Treatment
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* Biological: Pembrolizumab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to provide written informed consent/assent for the trial. Be 18 years of age on day of signing informed consent. Have measurable or evaluable disease, as defined in 2007 Revised Response Criteria for Malignant Lymphoma24 and have received at least two prior therapies. HL patients must not be currently eligible for autologous stem cell transplant. Be willing to provide either archived tumor tissue or tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation. Adequate Organ Function Laboratory Values: Absolute neutrophil count (ANC): ≥1,000 /microliter (mcL) Platelets: ≥75,000 / mcL Hemoglobin: ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) Serum creatinine OR: ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Serum total bilirubin: ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels: >1.5 ULN Aspartate aminotransferase (AST) / serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT): ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin: >2.5 mg/dL International Normalized Ratio (INR) or Prothrombin Time (PT): ≤1.5 X ULN unless subject 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 X ULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard. Female subject of childbearing potential should have two negative urine or serum pregnancy test, one at 10-14 days before first dose of study drug and another within 24 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: Is currently participating and receiving study therapy 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 treatment. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Has a known history of active Bacillus Tuberculosis (TB) Hypersensitivity to pembrolizumab or any of its excipients. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Has known history of, or any evidence of active, non-infectious pneumonitis. Has an active infection requiring systemic therapy. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C virus (HCV) (e.g., HCV Ribonucleic acid (RNA) [qualitative] is detected), or other active viral hepatitis. Patients with treated and resolved hepatitis B or C are eligible. Patients with active liver disease, except liver abnormalities directly attributable to lymphoma are ineligible, Has received a live vaccine within 30 days of planned start of study therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab and Lenalidomide<br>An intravenous infusion of 200 mg of pembrolizumab (MK3475) once every 3 weeks for a total of 4 infusions Lenalidomide at either 15 mg, 10 mg or 20 mg (depending on which cohort patients are enrolled in) days 1-14 every 21 days | Biological: Pembrolizumab<br> <br> * Other names: Keytruda;Drug: Lenalidomide<br> <br> * Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess Safety and Tolerability of the Combination of Pembrolizumab and Lenalidomide (Number of Drug Related Adverse Events) | Assessing the number of drug related adverse events at each dose level of lenalidomide | up to 2 years | 
| Estimate Overall Response Rate (ORR) | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment | up to 2 years | 
| Estimate Complete Response Rate (CR) | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment | up to 2 years | 
| Estimate Partial Response Rate (PR) | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate the ORR (CR, PR) for Combination Within & Across Dose Levels of Lenalidomide | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment. | up to 2 years | 
| Estimate Stable Disease (SD) for Combination Within & Across Dose Levels of Lenalidomide | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment. Kaplan-Meir methodology will be used to estimate median PFS and Overall Survival (OS). | up to 2 years | 
| Estimate Progression Free Survival (PFS) for Combination Within & Across Dose Levels of Lenalidomide | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment. Kaplan-Meir methodology will be used to estimate median PFS and OS. | up to 2 years | 
| Estimate Clinical Benefit (Including SD) for the Combination | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment. Kaplan-Meir methodology will be used to estimate median PFS and OS. | up to 2 years | 
| Estimate Progression Free Survival (PFS) for the Combination | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment. Kaplan-Meir methodology will be used to estimate median PFS and OS. | up to 2 years | 
| Estimate Duration of Response (DOR) for the Combination | Assessment of lymphoma response (CR, PR or SD) and disease progression will be evaluated according to the Revised Response Criteria for Malignant Lymphoma. Overall response will be measured for all patients who complete one cycle of treatment. Kaplan-Meir methodology will be used to estimate median PFS and OS. | up to 2 years |