Personalized Autologous Transplant for Multiple Myeloma

Inclusion Criteria:

• Patient must have the clinical diagnosis of a plasma cell neoplasm requiring treatmentper the treating physician using the International Myeloma Working Group (IMWG) andWorld Health Organization (WHO) criteria as guidelines. This can include extraosseousplasmacytoma, monoclonal immunoglobulin deposition disease, and heavy-chain diseasesas these diagnoses, while rare, can be treated in part with autologous transplant
• If enrolling in phase A of this protocol, the patient
• must have received 2+ lines of therapy as defined by the IMWG; and
• Must have estimated glomerular filtration rate (eGFR) by Cockcroft-Gault > 40mL/min; and
• Be eligible and appropriate per the treating physician to receive 200 mg/m^2
• If enrolling in phase B of the protocol, the transplant must be part offirst line therapy to provide some level of homogeneity for toxicityassessment and preliminary efficacy
• Absolute neutrophil count (ANC) >= 1000/uL
• Platelet count >= 100,000
• Total bilirubin < 1.5 x institutional upper limit of normal (unless the patient has anestablished diagnosis of Gilbert's in which case total bilirubin < 3 mg/dL)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x theinstitutional upper limit of normal
• Left ventricular ejection fraction >= 45%
• Diffusion capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) > 50% of predicted value (correctedfor hemoglobin)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)is required for eligibility. Those patients with lower performance status based solelyon bone pain secondary to multiple myeloma are eligible
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancytest prior to starting therapy. The effects of protocol therapy on the developinghuman fetus are unknown. For this reason, FCBP and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior to studyentry and for the duration of study participation. Should a woman become pregnant orsuspect she is pregnant while she or her partner is participating in this study, sheshould inform her treating physician immediately. Men treated or enrolled on thisprotocol must also agree to use adequate contraception prior to the study, for theduration of study participation, and 3 months after completion of protocol therapyadministration. Female of childbearing potential (FCBP) is a sexually mature womanwho: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not beennaturally postmenopausal for at least 24 consecutive months (i.e., has had menses atany time in the preceding 24 consecutive months)
• The patient must be willing to comply with fertility requirements
• Ability to understand and the willingness to sign a written informed consent document
• Patients with a prior or concurrent malignancy whose natural history or treatment doesnot have the potential to interfere with the safety or efficacy assessment of theinvestigational regimen are eligible for this trial

Exclusion Criteria:

• Patients known to meet criteria for progressive disease or clinical relapse betweenscreening and planned melphalan infusion day -3
• Subject has any of the following cardiac abnormalities
• History of clinically significant cardiovascular disease with New York HeartAssociation class III or IV congestive heart failure or
• Severe non-ischemic cardiomyopathy or
• Myocardial infarction within the previous 6 months prior to starting studytreatment
• Unstable or poorly controlled angina
• Uncontrolled severe hypertension
• Clinically/hemodynamically significant arrythmias
• Severe uncontrolled cardiac arrhythmias (grade 3 or higher) or
• Clinically significant electrocardiogram (ECG) abnormalities includingcorrectedQT interval (QTc) > 480 msec
• Human immunodeficiency virus (HIV) positive EXCEPT if the patient meets all thefollowing: CD4 > 350 cells/mm^3, undetectable viral load, maintained on moderntherapeutic regimen utilizing non CYP interacting agents (e.g. excluding ritonavir),and no untreated acquired immune deficiency syndrome defining opportunisticinfections.
• Seropositive for hepatitis B surface antigen [HBsAg]) EXCEPT subjects with resolvedinfection (ie, subjects who are positive for antibodies to hepatitis B core antigen [antiHBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) must be screenedusing real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV)DNA levels. Those who are PCR positive will be excluded. Subjects with serologicfindings suggestive of HBV vaccination (antiHBs positivity as the only serologicmarker) AND a known history of prior HBV vaccination, do not need to be tested for HBVDNA by PCR
• Seropositive for hepatitis C except in the setting of a sustained virologic response [SVR], defined as without viremia for at least 12 weeks after completion of antiviraltherapy
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS) syndrome, amyloid light-chain (AL) amyloidosis, and Waldenstrommacroglobulinemia
• Concurrent medical condition or disease (eg, active systemic infection) that is likelyto interfere with study procedures or results, or that in the opinion of theinvestigator would constitute a hazard for participating in this study
• Known or suspected of not being able to comply with the study protocol (eg, because ofalcoholism, drug dependency, or psychological disorder) or the subject has anycondition for which, in the opinion of the investigator, participation would not be inthe best interest of the subject (eg, compromise their well-being) or that couldprevent, limit, or confound the protocol-specified assessments
• Pregnant women are excluded from this study because protocol therapy has the potentialfor teratogenic or abortifacient effects. Because there is an unknown but potentialrisk for adverse events in nursing infants secondary to protocol treatment of themother, breastfeeding should be discontinued