Pembrolizumab and External Beam Radiation Therapy in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03210662|
Recruitment Status : Recruiting
First Posted : July 7, 2017
Last Update Posted : May 21, 2021
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Primary Mediastinal (Thymic) Large B-Cell Lymphoma Recurrent Aggressive Non-Hodgkin Lymphoma Recurrent Mature T- Cell and NK-Cell Non-Hodgkin Lymphoma Recurrent Non-Hodgkin Lymphoma Recurrent T-Cell Non-Hodgkin Lymphoma Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma Refractory Aggressive Non-Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma Refractory T-Cell Non-Hodgkin Lymphoma Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma||Radiation: External Beam Radiation Therapy Biological: Pembrolizumab||Phase 2|
I. To determine the overall response rate (ORR) of pembrolizumab with concurrent fractionated external beam radiotherapy (EBRT) among patients with relapsed and refractory non-Hodgkin lymphoma (NHL).
I. To determine the safety of pembrolizumab with fractionated EBRT in patients with relapsed and refractory NHL.
II. To determine the overall response rate and complete response rate (CRR) of irradiated and non-irradiated lesions to treatment with concurrent pembrolizumab and fractionated EBRT in patients with relapsed and refractory NHL.
III. To determine the progression free survival (PFS) of pembrolizumab in combination with fractionated EBRT.
IV. To determine the overall survival (OS) of pembrolizumab in combination with fractionated EBRT.
V. To determine the duration of response of irradiated and non-irradiated lesions after concurrent pembrolizumab and fractionated EBRT.
I. To identify tumor and peripheral blood markers predictive of response to concurrent pembrolizumab and low to moderate dose EBRT in the setting of relapsed and refractory NHL.
II. To determine if a course of hypo-fractionated EBRT can improve response after progressive disease among patients treated with fractionated EBRT and pembrolizumab.
Beginning on day 1, patients undergo fractionated EBRT daily for 5 consecutive days a week for up to 12 or 22 treatments. Patients also receive pembrolizumab intravenously (IV) over 1 hour on day 2. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year and then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Pembrolizumab and Fractionated External Beam Radiotherapy in Patients With Relapsed and Refractory Non-Hodgkin Lymphoma|
|Actual Study Start Date :||November 1, 2017|
|Estimated Primary Completion Date :||May 19, 2024|
|Estimated Study Completion Date :||May 19, 2025|
Experimental: Treatment (EBRT, pembrolizumab)
Beginning on day 1, patients undergo fractionated EBRT daily for 5 consecutive days a week for up to 12 or 22 treatments. Patients also receive pembrolizumab IV over 1 hour on day 2. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
Radiation: External Beam Radiation Therapy
- Overall response rate of an unirradiated lesion to pembrolizumab with external beam radiation therapy [ Time Frame: At 3 months ]Response rate and its 95% confidence interval will be estimated for each patient cohort separately. The overall response (OR: complete response + partial response) of non-irradiated lesion(s) at three months and dose limiting toxicity (DLT) at one course (3 weeks) will be monitored simultaneously using the Bayesian stopping boundaries calculated based on beta-binomial distributions. Independence is assumed between OR and DLT.
- Complete response rate [ Time Frame: Up to 3 years ]Disease response will be assessed via revised Lugano classification for the response assessment of Hodgkin and non-Hodgkin lymphoma.
- Progression free survival [ Time Frame: Up to 3 years ]Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model may be used to include multiple covariates in the time-to-event analysis.
- Overall survival [ Time Frame: Up to 3 years ]Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important patient characteristics will be made using the log-rank test. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model may be used to include multiple covariates in the time-to-event analysis.
- Duration of response [ Time Frame: Up to 3 years ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Have at least one site of lymphomatous disease amenable to external beam radiation therapy (EBRT)
- Have pathologic confirmation of aggressive non-Hodgkin lymphoma (including diffuse large B cell lymphoma, transformed follicular lymphoma, transformed marginal zone lymphoma, primary mediastinal B-cell lymphoma, T cell lymphoma and NK T-cell lymphoma). Patients with indolent B cell lymphoma are excluded
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable disease (>= 1.5 cm in the longest diameter for nodal or extranodal disease)
- Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization
- Absolute neutrophil count (ANC) >= 1,000 /mcL (performed within 10 days of treatment initiation)
- Platelets >= 50,000 / mcL (performed within 10 days of treatment initiation)
- Hemoglobin >= 8 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation)
- Serum creatinine OR measured or calculated creatinine clearance (creatinine clearance should be calculated per institutional standard) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 x upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (performed within 10 days of treatment initiation)
- Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 10 days of treatment initiation)
- 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 (performed within 10 days of treatment initiation)
- Albumin >= 2.5 mg/dL (performed within 10 days of treatment initiation)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
- 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 (performed within 10 days of treatment initiation)
- 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 as outlined - contraception, for the course of the study through 120, corresponding to time needed to eliminate any Merck study treatment(s) and/or any active comparator/combination, plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
- Has had prior radiation therapy to the potential radiation target such that additional radiation therapy is considered unsafe by the treating radiation oncologist
- Has a history of allogeneic stem cell transplantation
- Has a diagnosis of active scleroderma or lupus or any other autoimmune disease that by the opinion of the treating radiation oncologist would put the patient at unacceptable risk of toxicity
- 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 within the past 3 years. 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) lymphoma or lymphomatous 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
- 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or 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 pre-screening or screening visit through 120 days after the last dose of trial treatment
- A woman of child bearing potential (WOCBP) who has a positive urine pregnancy test 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. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03210662
|Contact: Chelsea C. Pinnix, MDfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Chelsea C. Pinnix 713-563-2300|
|Principal Investigator: Chelsea C. Pinnix|
|Principal Investigator:||Chelsea C Pinnix||M.D. Anderson Cancer Center|
|Responsible Party:||M.D. Anderson Cancer Center|
|Other Study ID Numbers:||
NCI-2018-01123 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0341 ( Other Identifier: M D Anderson Cancer Center )
|First Posted:||July 7, 2017 Key Record Dates|
|Last Update Posted:||May 21, 2021|
|Last Verified:||May 2021|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Immunological