High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant

This pilot phase II trial studies how well giving high dose busulfan together with bortezomib works in treating patients with high risk multiple myeloma undergoing stem cell transplant. Drugs used in chemotherapy, such as busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cells growth. Giving busulfan together with bortezomib before a stem cell transplant may kill more cancer cells

PRIMARY OBJECTIVES:

I. To determine time to engraftment absolute neutrophil count (\> 0.5 x 10\^9/L for 3 consecutive days), and platelet (\> 20X 109\^/L for 3 consecutive days).

2. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).

3. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).

SECONDARY OBJECTIVES:

I. Incidence of myeloma progression in this high risk group of patients.

II. Incidence of transplant related mortality and morbidity.

III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).

IV. Incidence and severity of chronic GVHD.

V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.

I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 \& 2 years post transplant.

VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.

GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0.

After completion of study treatment, patients are followed up for up to 2 years.

Eligibility Criteria:
Inclusion Criteria:

* Ability to provide informed consent
* Karnofsky Performance Status (KPS) \>= 70
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Availability of a suitable allogeneic hematopoietic stem cell donor; minimum of human leukocyte antigen (HLA) 7/8 matched related or unrelated donor
* High risk multiple myeloma with poor prognostic features based on having one or more of the following criteria:
* Progressive disease after autologous transplant. No less than 3 months post auto transplant
* Progressive or stable disease after induction chemotherapy using the most potent myeloma agents Lenalidomide and/or Bortezomib
* Patients with high risk cytogenetic abnormalities documented on conventional cytogenetics or fluorescence in situ hybridization (FISH) (hypodiploidy, t(4:14), t(14:16) chromosome translocation, p53 and or complex cytogenetics) additionally, chromosome 13 deletion by standard cytogenetics
* Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test for women, as well as implementation of birth control for men and women

Exclusion Criteria:

* Patients with prior allogeneic transplant, or more than one prior autologous transplant for any medical reason
* Prior treatment with busulfan or gemtuzumab (Mylotarg ®) for any reason
* Patient with history of allergy to boron, mannitol, or bortezomib
* Creatinine clearance (CrCl) =\< 50 ml/min
* Ejection Fraction \< 50%
* Diffusion capacity of carbon monoxide (DLCO) \< 50% predicted
* Forced expiratory volume in 1 second (FEV1) \< 50% predicted
* Forced vital capacity (FVC) \< 50% predicted
* Patients with uncontrolled arrhythmia or uncontrolled heart disease at the screening time; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echo or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the principal investigator
* Liver enzymes \> 3 times upper limit normal
* Bilirubin \> 2 mg/dl (except Gilbert's disease)
* International normalized ratio (INR) \> 2
* Any previous history of liver failure, hepatitis, or cirrhosis
* Systemic Amyloidosis Known history of hepatitis B, C, human immunodeficiency virus (HIV) or any current uncontrolled infection
* Grade \> I neuropathy
* Women who are pregnant or lactating
* Current or history of alcohol or drug abuse
* Use of other investigational agents within 30 days of enrollment to this study
* Any patient with ascites
* Any patient on home oxygen
* Any clinical findings on history or physical exam which would in the opinion of the treating physician or principal investigator preclude the patient from participating in the study