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 beencarefully considered to ensure the safety of the study participants and that theresults of the study can be used. It is imperative that participants fully meet alleligibility criteria.

2. Signed Written Informed Consent

• Participants must be able to give self-consent and then sign and date anInstitutional Review Board (IRB)/Independent Ethics Committee (IEC)-approvedwritten informed consent in accordance with local regulatory and institutionalguidelines. This consent must be obtained before the performance of anyprotocol-related procedures that are not considered part of normal participantcare.

• 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

3. 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 caretreatment 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 maximaldimension. Tumors larger than 65 cc can be partially treated but the wholetumor should receive at least the minimal prescribed dose confirmed by thestudy team. v) Participants must have an Eastern Cooperative Oncology Group performance statusthat is greater than or equal to 2 vi) Adequate organ function, as defined by labvalues that will be confirmed by the study doctor.

2. Age and Reproductive Status

• Participants must be males and females ≥ 18 years of age at the time ofinformed consent.

• Participants who are women of childbearing potential (WOCBP) must have anegative serum or urine pregnancy test within 72 hours prior to the start ofstudy.c) Participants who are women must not be breastfeeding. d) Participants whoare women of childbearing potential must agree to follow instructions formethod(s) of contraception for the duration of treatment with study drug(s) andup to 5 months post last dose of study drug(s).e) Participants who are women of childbearing potential who are continuouslynot heterosexually active are exempted from contraceptive requirements butstill must undergo pregnancy testing as described in this section.f) Participants who are males and who are sexually active with women ofchildbearing potential must agree to follow instructions for method(s) ofcontraception for the duration of treatment with study drug(s) and up to 7months post last dose of study drug(s). In addition, male participants must bewilling to refrain from sperm donation during this time.g) Participants who are azoospermic males are exempt from contraceptiverequirements.

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 13or Mirels' score less than 9 prior to starting radiation treatment

• Participants must not receive any concurrent anti-myeloma or systemic therapy ofany 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 thiscriterion and may qualify for the study. ii) Note: if subject received major surgery, they must have recovered adequatelyfrom the toxicity and/or complications from the intervention prior to startingtherapy. iii) Note: subjects with any grade alopecia are an exception to this criterion andmay 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 tobe treated with radiation.

• Participants who have had prior cytotoxic chemotherapy must not receive thattherapy within 2 weeks of the initiation of radiation

• Participants who have had prior anti-cancer monoclonal antibody (mAb) or othersmall molecules must not receive that therapy within 7 days of the initiation ofradiation

• Participants must not have a known additional malignancy that could confuseanalysis of on-study treatment. Inclusion of all study participants with more thanone malignancy must be discussed and approved by the PI.

• Participants must not have a known history of non-infectious pneumonitis thatrequired 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 ofthe treating investigator.

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

• Is pregnant or breastfeeding, or expecting to conceive or father childrenwithin the projected duration of the trial, starting with the screening visitthrough 120 days after the last dose of trial treatment.

• If known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C is detectedthen patient is not eligible for treatment of liver lesions

• Participants must not have had uncontrolled or significant cardiovasculardisease including, but not limited to, any of the following:

• Myocardial infarction or stroke/transient ischemic attack within the past 6 months

• Uncontrolled angina within the past 3 months

• Any history of clinically significant arrhythmias (such as ventriculartachycardia, ventricular fibrillation, or torsades de pointes)

• History of other clinically significant heart disease (e.g.cardiomyopathy, congestive heart failure with New York Heart Associationfunctional classification III to IV, pericarditis, significant pericardialeffusion, or myocarditis)

• Cardiovascular disease-related requirement for daily supplemental oxygentherapy.

• Participants may not concomitantly use statins while on study. However, apatient using statins for over 3 months prior to study drug administration andin stable status without creatine kinase (CK) rise may be permitted to enroll.

• Participants may not have current or history of clinically significant muscledisorders (e.g. myositis), recent unresolved muscle injury, or any conditionknown to elevate serum creatine kinase (CK) levels.

• Participants must not be prisoners or be involuntarily incarcerated.

• Participants must not be compulsorily detained for treatment of either apsychiatric or physical (e.g., infectious disease) illness. Eligibility criteria for this study have been carefully considered to ensure thesafety of the study participants and that the results of the study can be used. Itis imperative that participants fully meet all eligibility criteria.