The purpose of this study is to evaluate the safety and tolerability associated with the combination of ATRA/celecoxib/itraconazole as maintenance therapy given after an autologous stem cell transplant in relapsed multiple myeloma patients.

Primary objective:

To evaluate safety and tolerability associated with the combination of ATRA/ celecoxib/itraconazole given after a salvage transplant for relapsed myeloma in 25 patients in a cycle schedule consisting of three weeks of treatment followed by a rest period of two weeks for a total of five cycles. Subjects will be evaluable only if they have received at least one dose of maintenance treatment. The salvage transplant is not part of this study.

Secondary objective:

To explore changes in frequency and molecular signature in the multiple myeloma stem cell (MMSC) fraction based on flow-cytometric assays and gene expression profiling before and after the experimental treatment and to correlate outcome with expression levels of RARα2 at time of relapse.

Inclusion Criteria:

• Diagnosis of relapsed multiple myeloma
• Recent salvage transplant (≤ 6 months but ≥ 45 days post-transplant prior to study enrollment) for relapse
• 18-75 years of age at the time of study entry
• Platelet count ≥70K/mm3 un-transfused
• Resolution of all transplant-related toxicity to ≤ grade 2 per CTCAE v.4
• Left ventricular ejection fraction as measured by ECHO or MUGA should be ≥ 40%
• Creatinine of ≤ 2 mg/dl and a calculated GFR of >50mL/min/1.73m2
• A total bilirubin, ALT, AST, and alkaline phosphatase of ≤ 2 ULN
• Performance status of 0-2 based on the ECOG criteria. Patients with performance status 3 or 4, based solely on bone pain, are also eligible, provided that there is a source document to verify this
• Prospective study participants must be informed of the investigational nature of the study and must have signed an IRB-approved informed consent form in accordance with institutional and federal guidelines

Exclusion Criteria:

• Prior allogeneic transplant
• Greater than grade 2 motor neuropathy or greater than grade 3 sensory neuropathy at screening
• Uncontrolled diabetes
• Recent (< 6 months) myocardial infarction, unstable angina, CABG or stent placement in the last 2 years, difficult-to-control congestive heart failure, uncontrolled hypertension (systolic blood pressure > 160 mm or a diastolic BP > 110 mm under normal conditions and while on appropriate anti-hypertensive medications), or difficult- to-control cardiac arrhythmias
• Evidence of QT prolongation and/or torsades de pointes (TdP) on EKG.
• Any co-morbid condition that poses a greater threat to the patient's life expectancy than the recurrent myeloma
• No concurrent malignancy with a life expectancy of less than two years, or one that requires ongoing chemotherapeutic intervention at screening
• Presence of an infection that requires intravenous antibiotics
• Pregnant or nursing females. Any patient of reproductive potential may not participate unless he/she has agreed to use an effective contraceptive method as covered during the informed consent process
• Known history of an HIV seropositive test