Hypofractionation (Radiation) Trial for Multiple Myeloma

Inclusion Criteria: \- For entry into the study, the following criteria must be met prior to dosing on Day 1. No exceptions will be granted. Eligibility criteria for this study have been carefully considered to ensure the safety of the study participants and that the results of the study can be used. It is imperative that participants fully meet all eligibility criteria. 1. Signed Written Informed Consent * Participants must be able to give self-consent and then sign and date an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent in accordance with local regulatory and institutional guidelines. This consent must be obtained before the performance of any protocol-related procedures that are not considered part of normal participant care. * Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study. 2. Type of Participant and Disease Characteristics 1. General inclusion criteria: * Men or women ≥ 18 years of age. * Have clinically confirmed relapsed/refractory Multiple Myeloma with up to 5 osseous lesions that can be treated with radiation therapy (SINS score ≤ 13 or Mirels' score ≤ 9) iii) Have undergone appropriate standard of care treatment options (in the opinion of the treating investigator). iv) Participants must have measurable disease as defined by RECIST Version 1.1, including at least one tumor lesion that meets criteria for radiation. 1. . 0.25 cc to 65 cc of viable tumor approximately 5 cm in maximal dimension. Tumors larger than 65 cc can be partially treated but the whole tumor should receive at least the minimal prescribed dose confirmed by the study team. v) Participants must have an Eastern Cooperative Oncology Group performance status that is greater than or equal to 2 vi) Adequate organ function, as defined by lab values that will be confirmed by the study doctor. 3. Age and Reproductive Status * Participants must be males and females ≥ 18 years of age at the time of informed consent. * Participants who are women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to the start of study. c) Participants who are women must not be breastfeeding. d) Participants who are women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) and up to 5 months post last dose of study drug(s). e) Participants who are women of childbearing potential who are continuously not heterosexually active are exempted from contraceptive requirements but still must undergo pregnancy testing as described in this section. f) Participants who are males and who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) and up to 7 months post last dose of study drug(s). In addition, male participants must be willing to refrain from sperm donation during this time. g) Participants who are azoospermic males are exempt from contraceptive requirements. Investigators shall counsel women of childbearing potential , and male participants who are sexually active with women of childbearing potential , on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of \< 1% when used consistently and correctly. Exclusion Criteria: 1. Target Population • Participants must not have SINS (spinal instability neoplastic score) less than 13 or Mirels' score less than 9 prior to starting radiation treatment • Participants must not receive any concurrent anti-myeloma or systemic therapy of any form. • Participants who have not recovered (i.e. greater than grade 1 or at baseline) from adverse events due to a previously administered agent will be excluded. Participants may receive concurrent steroids. i) Note: subjects with greater than grade 2 neuropathy are an exception to this criterion and may qualify for the study. ii) Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. iii) Note: subjects with any grade alopecia are an exception to this criterion and may qualify for the study • Participants must not have had prior radiation therapy (defined as less than 10 percent of prior prescription dose) to the area planning to be treated with radiation. • Participants who have had prior cytotoxic chemotherapy must not receive that therapy within 2 weeks of the initiation of radiation • Participants who have had prior anti-cancer monoclonal antibody (mAb) or other small molecules must not receive that therapy within 7 days of the initiation of radiation • Participants must not have a known additional malignancy that could confuse analysis of on-study treatment. Inclusion of all study participants with more than one malignancy must be discussed and approved by the PI. * Participants must not have a known history of non-infectious pneumonitis that required steroids for treatment. * Participants must not have evidence of interstitial lung disease. * Participants must not have a current seizure disorder. * Participants must not have 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 pregnan