Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Tandem autologous stem cell transplant; Cisplatin; Doxorubicin; Cyclophosphamide; Etoposide; Bortezomib; Thalidomide; Melphalan
Intervention description: Given PO; Given IV; Given IV; Given IV or PO; Given IV; Given IV; Given PO; Given IV
Intervention MeSH terms: Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan; Doxorubicin; Liposomal doxorubicin; Etoposide; Etoposide phosphate; Bortezomib
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: 80 Years
Healthy volunteers: No
Keywords: multiple myeloma; POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes); amyloidosis; bone marrow transplant; autologous

Summary:

      This study is designed to decrease toxicity associated with prior tandem transplant protocols
      by reducing the intensity of induction, consolidation and maintenance therapy, while
      increasing event-free survival by adding bortezomib (Velcade®), thalidomide, gemcitabine and
      carmustine to the transplant regimens to down-regulate the rescue of myeloma cells by the
      micro-environment and to prevent DNA repair post high-dose alkylating agent therapy. By
      reducing drug resistance, it is hoped that 3-year event-free survival will be increased
      significantly when compared to Total Therapy II. Additionally, participants will have the
      option of providing biospecimens for a sub-study evaluating gene expression profiling at
      specific timepoints to better understand drug-resistance in myeloma, and to determine whether
      there are genes or gene products in the resistant population that can be targeted by novel
      therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants must have had a diagnosis of symptomatic MM, MM + amyloidosis, or POEMS
             (osteosclerotic myeloma: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal
             protein, Skin changes) requiring treatment. Participants with a previous history of
             smoldering myeloma will be eligible if there is evidence of progressive disease
             requiring chemotherapy. Note that study participants do not need to have active
             disease at the time of study entry, as participants may have received up to 12 months
             of prior chemotherapy, which might have induced a response.

          2. Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE
             and/or urinary kappa or lambda light chain, Bence-Jones protein, or Free Kappa Light
             Chain or Free Lambda Light Chain) in order to evaluate response. Non-secretory
             participants are eligible provided the participant has > 20% plasmacytosis OR multiple
             (>3) focal plasmacytomas or focal lesions on MRI.

          3. Participants must have received no more than 12 months of prior chemotherapy for this
             disease. Participants may have received prior radiotherapy provided approval has been
             obtained from the PI.

          4. Participants must not have had a prior transplant.

          5. Participants must be 18-80 years of age at the time of study entry.

          6. Ejection fraction by ECHO or MUGA of ≥ 40% performed.

          7. Participants must have adequate pulmonary function studies, > 50% of predicted on
             mechanical aspects (FEV1, FVC) and diffusion capacity (DLCO) > 50% of predicted
             (adjusted for hemoglobin). If the participant is unable to complete pulmonary function
             tests due to disease related pain or condition, a participant may still be enrolled
             provided that the PI or enrolling investigator documents that the participant is a
             transplant candidate.

          8. Participants must have a creatinine < 3 mg/dl and a calculated creatinine clearance
             >30mL/min. The Cockroft-Gault equation may be used to obtain calculated creatinine
             clearance.

          9. Participants must have a performance status of 0-2 based on ECOG criteria.
             Participants with a poor performance status (3-4)based solely on bone pain will be
             eligible, provided there is documentation to verify this.

         10. Participants must sign the most current IRB-approved study ICF (Informed Consent
             Form).

        Exclusion Criteria:

          1. Prior autologous or allogeneic transplant.

          2. Platelet count < 30 x 109/L, unless myeloma-related. If MM-related, the enrolling
             investigator must document this.

          3. > grade 3 neuropathy.

          4. Known hypersensitivity to bortezomib, boron, or mannitol.

          5. Uncontrolled diabetes.

          6. Recent (< 6 months) myocardial infarction, unstable angina, difficult to control
             congestive heart failure, uncontrolled hypertension, or difficult to control cardiac
             arrhythmias.

          7. Participants must not have light chain deposition disease-related renal failure or
             creatinine >3 mg/dl.

          8. Participants must not have a concurrent malignancy unless it can be adequately treated
             by surgical, non-chemotherapeutic intervention. Participants may have a history of
             prior malignancy, provided that he/she has not had any treatment within 365 days of
             study entry AND that life expectancy exceeds 5 years at the time of study entry.

          9. Participants must not have life-threatening co-morbidities.

         10. Women of child-bearing potential must have a documented negative pregnancy test
             documented within one week of study entry. Women and men of reproductive potential may
             not participate unless they have agreed, by signing the study ICF, to use effective
             contraceptive method(s) as outlined in that form.