Busulfan, Melphalan, and Bortezomib Before First-Line Stem Cell Transplant in Treating Patients With Multiple Myeloma
Condition: DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Busulfan; Melphalan; Bortezomib; Autologous Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation
Intervention description: Given IV; Given IV; Given IV; Undergo autologous PBSCT; Undergo autologous PBSCT
Intervention MeSH terms: Bortezomib; Melphalan; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 72 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well busulfan, melphalan, and bortezomib before first-line
      stem cell transplant works in treating patients with multiple myeloma. Giving chemotherapy
      before a peripheral blood stem cell transplant may stop the growth of cancer cells by
      stopping them from dividing or killing them. After treatment, stem cells are collected from
      the patient's blood and stored. The stem cells are then returned to the patient to replace
      the blood-forming cells that were destroyed by the chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed multiple myeloma

          -  Measurable disease must be present as defined by protein criteria (quantifiable
             M-component in serum, urine or serum free light chains) in order to evaluate response
             as per IMWG; non-secretory patients are eligible provided the patient has > 20%
             plasmacytosis OR multiple (> 3) focal plasmacytomas or focal lesions on magnetic
             resonance imaging (MRI)

          -  Patients must have received induction chemotherapy for myeloma, but not more than 12
             months of prior chemotherapy for this disease, and must be eligible for the first
             planned autologous transplant

          -  A minimum stem cell dose of 2.0 x 10^6 cluster of differentiation 34-positive (CD34+)
             cells/kg has been collected

          -  Life expectancy of greater than 12 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Leukocytes >= 3,000/mcL (unless myeloma related)

          -  Absolute neutrophil count >= 1,500/mcL (unless myeloma related)

          -  Platelets >= 50,000/mcL (unless myeloma related)

          -  Total bilirubin =< 2 x institutional upper limit of normal unless 2nd to Gilbert's
             disease

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3 x institutional upper limit of normal

          -  Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Ejection fraction by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) >=
             40% performed within 60 days prior to registration

          -  Patients must have adequate pulmonary function studies: > 50% of predicted on
             mechanical aspects (forced expiratory volume in one second [FEV1], forced vital
             capacity [FVC]) and diffusion capacity (diffusing capacity of the lung for carbon
             monoxide [DLCO]) > 50% of predicted, within 60 days of registration; if the patients
             is unable to complete pulmonary function tests due to multiple myeloma (MM) related
             pain or condition, exception may be granted if the principal investigator (PI)
             documents that the patient is a candidate for high dose therapy

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             at least six months following the stem cell transplantation; should a woman become
             pregnant or suspect she is pregnant while participating in this study, she should
             inform her treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier

          -  Prior treatment history of autologous hematopoietic stem cell transplant (HSCT) or
             high-dose chemotherapy with stem cell rescue for any medical reason, not limited to
             myeloma treatment

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to or other agents used in the study, such as busulfan, melphalan,
             bortezomib, boron, or mannitol

          -  Grade 2 or greater peripheral neuropathy within 14 days prior to enrollment

          -  Unresolved grade >= 3 non-hematologic toxicity from previous therapy; patients with
             grade 2 toxicity will be eligible at the discretion of the PI

          -  Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma
             in situ; cancer treated with curative intent < 5 years will not be allowed unless
             approved by the PI; cancer treated with curative intent > 5 years will be allowed

          -  Patients must not have significant co-morbid medical condition

          -  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; patients must not have suffered recent (< 6 months) myocardial
             infarction, unstable angina, difficult to control congestive heart failure,
             uncontrolled hypertension, or difficult to control cardiac arrhythmias

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with busulfan

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Patients found to have an active hepatitis B infection (hepatitis B surface antigen +)
             are not eligible unless they meet ONE of the following criteria:

               -  Patient is able to start dual anti-hepatitis (Hep) B therapy prior to enrollment
                  with adefovir and telbivudine

               -  Patient is already on dual anti-hepatitis B therapy

               -  Consultation and co-management with a hepatitis expert regarding hepatitis B
                  treatment is strongly encouraged before and during the trial

          -  Patients, who are positive for hepatitis B core antibody, but negative for the
             hepatitis B surface antigen, should be started on lamivudine 100 mg daily until at
             least 3 months post stem cell transplant