UARK 2003-33, Total Therapy III
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma
Intervention: Velcade; Thalidomide
Intervention description: Two cycles of induction on days 1,4,8,11 at 1.0mg/m^2. Two cycles of consolidation on days 1,4,8,11 at 1.0mg/m^2. Maintenance year one 1.0mg/m^2 1,4,8,11 q 28 days.; Two cycles of VDTPACE 200mg thal days 4-7(cycle 1)and days 1-4 cycle 2 interim Thal 50mg qd between VTDPACE cycles and between cycle 2 and transplant. Thal 100mg between transplants d/c 7 days prior to each transplant. Consolidation therapy cycles 3 and 4 VDTPACE 200mg days 1-4 both cycles. Interim maintenance to maintenance 100mg qd. Maintenance year 1 thal 100mg qd. Maintenance years 2 and 3 Thal 100mg qd.
Intervention MeSH terms: Thalidomide; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 303.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      There have been two previous Total Therapy studies for multiple myeloma (MM) at the Myeloma
      Institute for Research and Therapy (MIRT): Total Therapy I (from 1989 through 1994) and Total
      Therapy II (from 1996 to 2004). Results have shown that patients treated on these studies had
      better outcomes (meaning patients have lived longer and had better responses to treatment)
      when compared to patients treated with standard chemotherapy.

      With this new study, Total Therapy III, researchers will take what they have learned from the
      first two studies and add new treatment strategies to try to improve the outcomes even more,
      especially for patients with chromosome abnormalities.
    

Eligibility criteria:

        Induction Inclusion Criteria:

          -  Patients must have newly diagnosed active MM requiring treatment. Patients with a
             previous history of smoldering myeloma will be eligible if there is evidence of
             progressive disease requiring chemotherapy.

          -  Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE
             and/or urinary kappa or lambda light chain or Bence Jones protein) in order to
             evaluate response. Non-secretory patients are eligible provided the patient has > 20%
             plasmacytosis or multiple (>3) focal plasmacytomas on MRI or diffuse hyperintense
             signal on STIR images in the absence of hematopoietic growth factors.

          -  Patients must have received no more than one cycle of prior chemotherapy for this
             disease. Patients may have received prior radiotherapy provided approval has been
             obtained by the Principal Investigator.

          -  Patients must be < or = 75 years of age at the time of initial registration.

          -  Ejection fraction by ECHO or MUGA >40% performed within 60 days prior to registration.

          -  Patients must have adequate pulmonary function studies > or = 50% of predicted on
             mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > or =50% of
             predicted, within 60 days of registration. If the patient is unable to complete
             pulmonary function tests due to MM related pain or condition, there must be a
             pulmonary consult documenting that the patient is a candidate for high dose therapy.

          -  Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a
             poor performance status (3-4), based solely on bone pain, will be eligible.

          -  All patients must be informed of the investigational nature of this study and must
             have signed an IRB-approved informed consent in accordance with institutional and
             federal guidelines.

        Induction Exclusion Criteria:

          -  Platelet count < 30 x 10^9/L, unless myeloma-related

          -  ANC < 1.0 X 10^9/L, unless myeloma-related

          -  Grade > or =2 peripheral neuropathy

          -  Hypersensitivity to bortezomib, boron, or mannitol

          -  Uncontrolled diabetes.

          -  Recent (< or =6 months) myocardial infarction, unstable angina, difficult to control
             congestive heart failure, uncontrolled hypertension, or difficult to control cardiac
             arrhythmias.

          -  Evidence of chronic obstructive or chronic restrictive pulmonary disease.

          -  Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, in situ cervical cancer, or other cancer for which the patient has been
             disease free for at least three years.

          -  Patients must not have significant co-morbid medical conditions or uncontrolled life
             threatening infection.

          -  Pregnant or nursing women. Women of child-bearing potential must have a negative
             pregnancy test documented within one week of registration. Women and men of
             reproductive potential may not participate unless they have agreed to use an effective
             contraceptive method.