A Phase 2 Study Incorporating Bone Marrow Microenvironment (ME) Co-Targeting Bortezomib Into Tandem Melphalan-Based Autotransplants With DT PACE for Induction/Consolidation and Thalidomide + Dexamethasone for Maintenance
- 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
- 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
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
- 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
- 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.