Phase II Study of V-BEAM Conditioning Regimen Prior to Second Autologous Stem Cell Transplantation
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Bortezomib; Carmustine; Etoposide; Cytarabine; Melphalan; Stem cell infusion
Intervention MeSH terms: Cytarabine; Etoposide; Bortezomib; Melphalan; Carmustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      BEAM regimen (BCNU, etoposide, cytarabine, and melphalan) is the most commonly used
      conditioning regimen for relapsed/refractory lymphoma patients needing autologous stem cell
      transplantation. Since these components are all effective in myeloma and bortezomib has shown
      promising results in the transplant setting, here the investigators propose a phase II study
      to investigate the combination of bortezomib and BEAM as a new conditioning regimen for
      patients who relapse or progress after the first autologous transplantation and for whom a
      second autologous transplant is considered.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must have a histologically confirmed diagnosis of multiple myeloma.

          -  Patient must have received a prior autologous stem cell transplantation with melphalan
             conditioning for multiple myeloma with subsequent disease progression and repeat
             autologous stem cell transplantation is deemed appropriate by the treating physicians.

          -  Patient must receive induction chemotherapy including 2 to 4 cycles of anti-myeloma
             therapy including bortezomib, with or without immune modulating agents and/or
             corticosteroids, Completion of induction therapy will occur within 30 days of first
             study drug dose.

          -  Patient must have ≥ 2x106/kg CD34+ autologous stem cells available for
             transplantation.

          -  Patient must be ≥ 18 years of age.

          -  Patient must have life expectancy of greater than 6 months.

          -  Patient must have an ECOG performance status ≤ 2 or Karnofsky performance status ≥ 60%
             (see Appendices A and B)

          -  Patient must have normal bone marrow and organ function as defined below within 14
             days prior to first study drug dose (conditioning regimen):

               -  Absolute neutrophil count ≥500/mm3

               -  Platelets ≥ 50,000/mm3

               -  Hemoglobin ≥ 8 g/dl

               -  Total bilirubin ≤ 1.5 x IULN

               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

               -  Creatinine clearance (Appendix C) ≥30 mL/min/1.73m2

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) prior to study entry through
             Day +100 visit. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she must inform her treating physician immediately.

          -  Patient must be able to understand and willing to sign an IRB approved written
             informed consent document.

        Exclusion Criteria:

          -  Patient must not be refractory to induction therapy. Refractory is defined as disease
             progression while on therapy or within 30 days following completion of therapy.

          -  Patient must not have had disease progression requiring active treatment within 12
             months of previous autologous stem cell transplant. Maintenance therapy is not
             considered active treatment.

          -  Patient must not have peripheral neuropathy ≥ grade 3 based on NCI CTCAE v 4.0
             (Appendix D).

          -  Patient must not be receiving renal replacement therapy, hemodialysis, or peritoneal
             dialysis.

          -  Patient must not have another concurrent malignancy requiring treatment.

          -  Patient must not be receiving any other investigational agents within 14 days prior to
             the first dose of study drug.

          -  Patient must not have known brain metastases. Patients with known brain metastases
             must be excluded from this clinical trial because of their poor prognosis and because
             they often develop progressive neurologic dysfunction that would confound the
             evaluation of neurologic and other adverse events.

          -  Patient must not have a history of allergic reactions attributed to compounds of
             similar chemical or biologic composition to bortezomib, carmustine, etoposide,
             cytarabine, and melphalan, or other agents used in the study.

          -  Patient must not have an uncontrolled intercurrent illness including, but not limited
             to, ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Patient must not be pregnant and/or breastfeeding.

        Inclusion of Women and Minorities

        -Both men and women and members of all races and ethnic groups are eligible for this trial.