High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant
Condition: Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: pharmacological study; tacrolimus; sirolimus; anti-thymocyte globulin; fludarabine phosphate; busulfan; bortezomib; allogeneic hematopoietic stem cell transplantation; laboratory biomarker analysis
Intervention description: Correlative studies; Given IV; Given PO; Given IV; Given IV; Given IV; Given IV; Undergo allogeneic HSCT; Correlative studies
Intervention MeSH terms: Sirolimus; Fludarabine; Fludarabine phosphate; Bortezomib; Busulfan; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Immunoglobulins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      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
    

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