Subcutaneous (SC) Bortezomib-Regimens for Patients With RR MM Failing Prior IV Bortezomib-Containing Regimens
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Subcutaneous bortezomib
Intervention description: Bortezomib will be administered SC at a dose of 1.0 mg/m2. Doses are to be administered on days 1, 4, 8, and 11 of a 28-day cycle. All other drugs used in combination with the SC bortezomib as well as their doses and schedules will be at the discretion of the Principal Investigator.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Relapsed; Refractory; Bortezomib; Subcutaneous; Oncotherapeutics

Summary:

      This is a phase 2, multicenter, open label, nonrandomized study for patients with MM who will
      receive treatment with a SC bortezomib-containing combination regimen that does not contain
      thalidomide or vincristine. The patients will be required to have received a prior IV
      bortezomib containing combination regimen that did not contain thalidomide or vincristine and
      that differs from the SC bortezomib-containing one. In between the time that the patient
      received the IV bortezomib-based combination regimen and enrollment onto this study, patients
      may have received other non-bortezomib-based regimens as long as these treatments did not
      contain thalidomide or vincristine. This study will enroll patients who have relapsed or have
      become refractory to their prior IV-administered bortezomib-containing combination regimen as
      demonstrated by progressive disease while on or following that regimen. Patients must have
      received 4 doses of a minimum of 1.0 mg/m2 of bortezomib administered IV in no more than 4
      weeks per cycle. Patients must have received at least one cycle meeting this definition and
      have shown progressive disease to be considered eligible. Patients who have relapsed or have
      become refractory to their most recent IV bortezomib-containing combination regimen are
      eligible regardless of when they received that regimen, as long as they meet the above
      criteria.

      The study will consist of a screening period, followed by up to eight open label treatment
      cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a
      follow-up period.
    

Eligibility criteria:

        Inclusion Criteria (Crit.):

          1. Has a diagnosis of MM based on the following:

             Major crit.:

               1. plasmacytomas on tissue biopsy

               2. bone marrow plasmacytosis (> 30% plasma cells)

               3. m-spike on serum electrophoresis IgG > 3.5 g/dL or IgA > 2.0 g/dL; kappa or
                  lambda light chain excretion > 1 g/day on 24 hour urine protein electrophoresis

             Minor crit.:

               1. bone marrow plasmacytosis (10% to 30% plasma cells)

               2. monoclonal Ig present but of lesser magnitude than given under major crit.

               3. lytic bone lesions

               4. normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL

             Any of the following sets of crit. will confirm the diagnosis of MM:

               -  any 2 of the major crit.

               -  major criterion 1 plus minor criterion 2, 3, or 4

               -  major criterion 3 plus minor criterion 1 or 3

               -  minor crit. 1, 2, and 3, or 1, 2, and 4

          2. MM with measurable disease, defined as:

               -  a m-spike on serum electrophoresis of at least 0.5 g/dL and/or

               -  urine monoclonal protein levels of at least 200 mg/24 hours

               -  for patients without measurable serum and urine M-protein levels, an abnormal
                  free light chain ratio (normal value: 0.26 - 1.65)

          3. Currently has progressive MM:

               -  Relapsed following stabilization or a response to at least one IV bortezomib
                  (bort.) containing combination regimen that did not contain thalidomide or
                  vincristine or refractory defined as progressed while receiving that anti-myeloma
                  tx

               -  In between the IV bort.-based combination regimen and this study, the pt may have
                  received other non-bort.-based regimens as long as these treatments did not
                  contain thalidomide or vincristine

          4. Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care

          5. Age: ≥18 yrs at the time of consent

          6. Able to adhere to the study visit schedule and other protocol requirements

          7. ECOG performance status of ≤ 2 at study entry

          8. Life-expectancy > 3 mos

          9. Laboratory test results w/in these ranges at Screening and confirmed at enrollment
             prior to drug dosing on Cycle 1, Day 1:

               -  ANC ≥ 1.5 x 109/L; if the bone marrow is extensively infiltrated (> 70% plasma
                  cells) then ≥ 1.0 x 109/L

               -  Platelet count ≥ 75 x 109/L; if the bone marrow is extensively infiltrated (> 70%
                  plasma cells) then ≥ 50 x 109/L

               -  Hgb > 8 g/dL

               -  Calculated or measured CrCl of at least 30 mL/min. (see protocol)

               -  Total Bili ≥ 1.5 x ULN

               -  AST (SGOT) and ALT (SGPT) ≥ 3 x ULN ≥ 5 x ULN if hepatic metastases are present

               -  Serum potassium WNL

         10. Female pt is either postmenopausal for 1 year or greater before the screening visit,
             is surgically sterilized or if they are of childbearing potential, agree to practice 2
             effective methods of contraception from the time of signing the informed consent form
             through 30 days after the last dose of VELCADE, or agree to completely abstain from
             heterosexual intercourse.

         11. Male patients who agree to 1) practice effective barrier contraception during the
             entire study treatment period and through a minimum of 30 days after the last dose of
             study drug, or 2) completely abstain from heterosexual intercourse.

        Exclusion Criteria:

          1. POEMS syndrome

          2. PCL

          3. Primary amyloidosis

          4. Diagnosed or treated for another malignancy w/in 3 yrs of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

          5. ≤ Grade 2 peripheral neuropathy

          6. Pt had myocardial infarction w/in 6 months prior to enrollment or has NYHA Class III
             or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias,
             or electrocardiographic evidence of acute ischemia or active conduction system
             abnormalities.

          7. Severe hypercalcemia, i.e., serum calcium ≤ 12 mg/dL (3.0 mmol/L) corrected for
             albumin

          8. Undergone major surgery w/in 28 days prior enrollment or has not recovered from side
             effects of such therapy (see protocol)

          9. Received the following prior therapy:

               -  Thalidomide or vincristine alone or as part of a treatment regimen administered
                  between the last IV bort.-based regimen and Cycle 1, Day 1 on this study.
                  However, prior exposure to thalidomide or vincristine is allowed.

               -  Chemotherapy w/in 21 days of study drugs (6 weeks for nitrosoureas)

               -  Corticosteroids (>10 mg/day prednisone or equivalent) w/in 21 days of study drugs
                  unless steroids are being administered at that dose or greater as part of the new
                  regimen

               -  Immunotherapy or antibody therapy as well as lenalidomide, arsenic trioxide or
                  bort. w/in 21 days before study drugs

               -  Radiation therapy w/in 21 days before study drugs. (see protocol for exceptions)

               -  Use of any other experimental drug or therapy w/in 28 days of study drugs

         10. Participation in clinical trials with other investigational agents not included in
             this trial, w/in 14 days of the start of this trial and throughout the duration of
             this trial.

         11. Hypersensitivity to VELCADE (bort.), boron, or mannitol.

         12. Concurrent use of other anti-cancer agents or treatments

         13. Pregnant or lactating patients

         14. Serious medical or psychiatric illness

         15. Known positivity for HIV or hepatitis B or C