Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma
Pembrolizumab and Radiation Therapy in Patients With Relapsed or Refractory Multiple Myeloma
This pilot clinical trial studies the side effects of pembrolizumab and radiation therapy in
 treating patients with stage I-III multiple myeloma that has come back after a period of
 improvement or that does not respond to treatment. Monoclonal antibodies, such as
 pembrolizumab, may block cancer growth in different ways by targeting certain cells.
 Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving
 pembrolizumab and radiation therapy may work better in treating patients with stage I-III
 multiple myeloma.
PRIMARY OBJECTIVE:

 I. To evaluate the safety of concurrent single/low dose radiation therapy (radiotherapy) (8
 Gy/1fx) in combination with pembrolizumab in relapsed or refractory myeloma patients.

 SECONDARY OBJECTIVES:

 I. To characterize late toxicity (Common Terminology Criteria for Adverse Events [CTCAE] >
 grade 2 toxicity at 6 and 12 months) and the effect of radiation in combination with
 pembrolizumab on systemic response rates using international myeloma working group (IMWG)
 uniform response criteria for multiple myeloma at 6 months and 12 months.

 II. To assess changes in positron emission tomography/computed tomography (PET/CT) as a
 result of combining pembrolizumab and radiotherapy at 6 months and 12 months.

 OUTLINE:

 Patients undergo radiation therapy on day 1. Patients also receive pembrolizumab
 intravenously (IV) over 30 minutes on day 2 or 3. Courses with pembrolizumab repeat every 3
 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up at 30 days and then every 12
 weeks thereafter.
Inclusion Criteria:

 -  International Staging System (ISS) stage I-III multiple myeloma that has progressive,
 relapsed, or refractory disease

 -  Able to give informed consent

 -  Eastern Cooperative Oncology Group (ECOG) 0-1

 -  Relapsed and/or refractory myeloma; there is no minimum or maximum number of previous
 therapies that a patient may have received previously before being put on the current
 trial

 -  ≥ 1 osseous and/or extra-osseous lesion that can be radiated

 -  Candidate for pembrolizumab (as determined by physician, and adequate organ function)

 -  Candidate for radiotherapy (as determined by treatment physician); these patients can
 have symptomatic disease and/or asymptomatic disease; a minimum of one site of
 radiation is required to any osseous and/or any extra-osseous disease; radiation to
 any bony parts of the head and neck, skull, spine, ribs, and/or extremities are
 allowed; radiation to any bony part for documented lytic disease is allowed; radiation
 to any soft tissue plasmacytoma (including osseous and extra-osseous plasmacytoma) is
 allowed; the only exclusion criteria for radiation, is central nervous system (CNS)
 metastases

 -  Measurable myeloma disease (urine protein > 200 mg in 24 hours [hr] urine collection,
 serum free light chain ratio > 100 with an abnormal k/l ratio, serum M protein > 0.5
 g/dl); 12 of the 24 patients do not have to have measurable disease

 -  Negative urine pregnancy test within 2 weeks for female subjects; female subjects 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 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

 -  Abstinence is acceptable, if this is the usual life style and preferred
 contraception for the patient

 Exclusion Criteria:

 -  Previous anti-programmed cell death protein 1 (PD1) or anti-PD-L1

 -  Solitary plasmacytoma

 -  Smoldering (asymptomatic) multiple myeloma

 -  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

 -  Known history of active TB (Bacillus tuberculosis)

 -  Hypersensitivity to pembrolizumab or any of its recipients

 -  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)

 -  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)

 -  Known history of, or any evidence of active, non-infectious pneumonitis

 -  Active infection requiring systemic therapy

 -  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

 -  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

 -  Patients requiring radiation for CNS diseases are excluded (CNS defined as brain soft
 tissue/intra parenchymal metastases within the gray and white matter of the brain
 and/or for cerebrospinal fluid [CSF] disseminated disease, including leptomeningeal
 carcinomatous disease)

 -  Has a history of allogeneic stem cell transplantation