Pembrolizumab and Fractionated External Beam Radiotherapy (EBRT) in Patients With Non-Hodgkin Lymphoma (NHL)

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 70
• Participant gender: All

Summary

The goal of this clinical research study is to learn if the combination of external beam radiation therapy (EBRT) and pembrolizumab can help control relapsed (has come back) and refractory (has not responded to treatment) non-Hodgkin's Lymphoma (NHL). The safety of this combination will also be studied.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab
• Last Updated: 2017-07-05

Criteria

Inclusion Criteria:

1. Have at least one site of lymphomatous disease amenable to external beam radiation therapy (EBRT)

2. Have at least one non-contiguous lesions that is distinct from the radiation candidate lesion that is able to be evaluated radiographically or clinically.

3. Be willing and able to provide written informed consent/assent for the trial.

4. Be >/= 18 years of age on day of signing informed consent.

5. Have measurable disease (>/= 1.5 cm in the longest diameter for nodal or extranodal disease)

6. Be willing to provide 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. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.

7. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

8. Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of treatment initiation. *HEMATOLOGICAL: Absolute neutrophil count (ANC) = >/=1,500 /mcL; Platelets = >/=100,000 / mcL; Hemoglobin = >/=9 g/dL or >/=5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) *RENAL: Serum creatinine OR Measured or calculated creatinine clearance (creatinine clearance should be calculated per institutional standard) (GFR can also be used in place of creatinine or CrCl) =/=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN *HEPATIC: Serum total bilirubin =bilirubin levels > 1.5 ULN;

9. Inclusion #8 cont'd: aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransfaerase (ALT) serum glutamic pyruvic transaminase (SGPT) =Albumin = >/=2.5 mg/dL *COAGULATION: International Normalized Ratio (INR) or Prothrombin Time (PT) =as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) =receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

10. 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.

11. 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 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

12. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

1. Has had prior radiation therapy to the potential radiation target such that additional radiation therapy is considered unsafe by the treating radiation oncologist

2. Has a history of allogeneic stem cell transplantation

3. 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.

4. 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.

5. 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.

6. Has a known history of active Bacillus Tuberculosis (TB)

7. Hypersensitivity to pembrolizumab or any of its excipients

8. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e.,due to agents administered more than 4 weeks earlier.

9. 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.,baseline) from adverse events due to a previously administered agent. *Note: Subjects withstudy. **Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

10. 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.

11. 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.

12. 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.

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

14. Has an active infection requiring systemic therapy.

15. 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.

16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

17. 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.

18. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

19. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

20. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

21. 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.