Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant
Condition: Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: liposomal doxorubicin; bortezomib; dexamethasone; cyclophosphamide
Intervention description: Given IV; Given subcutaneously.; Given orally; Given IV
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bortezomib; Liposomal Doxorubicin; Dexamethasone; Cyclophosphamide; refractory multiple myeloma

Summary:

      This phase II trial is studying how well giving bortezomib together with liposomal
      doxorubicin hydrochloride, dexamethasone, and cyclophosphamide works in treating patients
      with multiple myeloma that relapsed after autologous stem cell transplant. Bortezomib may
      stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs
      used in chemotherapy, such as liposomal doxorubicin hydrochloride, dexamethasone, and
      cyclophosphamide, work in different ways to stop the growth of cancer cells, either by
      killing the cells or by stopping them from dividing. Giving bortezomib together with
      liposomal doxorubicin hydrochloride, dexamethasone, and cyclophosphamide may kill more cancer
      cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of multiple myeloma that was symptomatic at the time of initial diagnosis

          -  Must have met the following criteria at one point during the disease course:

               -  Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or
                  biopsy-proven plasmacytoma

               -  Symptomatic disease at initial diagnosis that prompted the initiation of therapy
                  as well as evidence of end-organ damage at the time of diagnosis, including at
                  least 1 of the following:

                    -  Anemia

                    -  Hypercalcemia

                    -  Bone disease (lytic bone lesions or pathologic fracture)

                    -  Renal dysfunction

          -  Disease relapsed < 12 months after autologous stem cell transplantation (SCT)

          -  Measurable disease, as defined by the presence of ≥ 1 of the following:

               -  Serum M-spike ≥ 1 g/dL

               -  Urine M-spike ≥ 200 mg/24 hours

               -  Involved free light chain (FLC) ≥ 10 mg/dL (provided the serum FLC is abnormal)

               -  Plasma cells ≥ 30%

          -  ECOG performance status 0-2

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  At least 14 days since prior palliative and/or localized radiotherapy

          -  Left ventricular ejection fraction (LVEF) normal by Echocardiography (ECHO) or
             multiple-gated acquisition (MUGA) scan

          -  Hemoglobin > 8 g/dL

          -  Platelet count ≥ 75,000/mm^3 (without transfusion support)

          -  Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (without use of growth factors)

          -  Creatinine < 2.5 mg/dL

          -  Direct bilirubin ≤ 1.5 mg/dL

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper
             limit of normal

          -  All tests below must be performed within 14 days prior to registration:

               -  Serum free light chain assay

               -  Kappa free light chain

               -  Lambda free light chain

          -  Prior malignancy allowed provided it was treated curatively and has not relapsed in 5
             years

               -  Patients with basal cell skin cancer, in situ cervical cancer, or prostate cancer
                  not requiring therapy are eligible

        Exclusion Criteria:

          -  Therapy for relapsed disease following SCT

          -  Known allergy to bortezomib or anthracyclines

          -  Prior allogeneic SCT

          -  Peripheral neuropathy ≥ grade 2 according to the Cancer Therapy Evaluation Program
             (CTEP) active version of the NCI Common Terminology Criteria for Adverse Events
             (CTCAE)

          -  Concurrent uncontrolled illness that would limit study compliance, including the
             following:

               -  Uncontrolled hypertension

               -  Symptomatic congestive heart failure

               -  Unstable angina

               -  Uncontrolled cardiac arrhythmia

               -  Uncontrolled psychiatric illness or social situation

               -  Active uncontrolled infection

          -  Prior doxorubicin hydrochloride exposure > 240 mg/m^2

          -  Active, uncontrolled seizure disorder

          -  Seizures within the past 6 months

          -  Pregnant or nursing