Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma
Condition: Extramedullary Plasmacytoma; Isolated Plasmacytoma of Bone; Light Chain Deposition Disease; Primary Systemic Amyloidosis; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Immunoglobulin Light-chain Amyloidosis; Amyloidosis
Intervention: dexamethasone; cisplatin; doxorubicin; cyclophosphamide; etoposide; bortezomib; thalidomide; melphalan; autologous stem cell transplant
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: 41.0
Sex: All
Minimum age: 65 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This phase II trial investigates whether patients greater than or equal to 65 years of age
      diagnosed with myeloma or another plasma cell malignancy will have better outcomes with
      transplant followed by maintenance therapy, as primarily measured by progression-free
      survival, versus non-transplant approaches.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have had a diagnosis of symptomatic multiple myeloma (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

          -  Protein criteria must be present at diagnosis (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) plasmacytomas or lesions on MRI at the time of
             diagnosis or study enrollment , OR the presence of lesions on PET/CT scan or skeletal
             survey at diagnosis or study enrollment.

          -  Participants must have received ≤12 months of prior chemotherapy for this disease
             without evidence of progressive disease with treatment. Participants may have received
             prior radiotherapy provided approval has been obtained from the PI. Participants with
             a history of radiation who have a platelet count <150,000 due to radiation (disease,
             chemo, and other factors have been ruled out) will be excluded from this study.

          -  Participants must not have had a prior transplant

          -  Participants must be 65-85 years of age at the time of study entry.

          -  Ejection fraction by echocardiogram (ECHO) or multigated acquisition scan (MUGA) of >=
             40% performed

          -  Participants must have adequate pulmonary function studies (PFTs), >= 50% of predicted
             on mechanical aspects (forced expiratory volume in 1 second [FEV^1}, forced vital
             capacity [FVC]) and diffusion capacity (diffusion capacity of the lung for carbon
             monoxide [DLCO]) >= 50% of predicted (adjusted for hemoglobin); if the participant is
             unable to complete pulmonary function tests (PFTs) due to disease-related pain or
             other circumstances that make it difficult to reliably perform PFTs, documentation of
             pulmonary function adequate for transplant will occur via a CT scan without evidence
             of major pulmonary disease, and arterial blood gas results

          -  Participants must have a creatinine < 3 mg/dl and a GFR >30mL/min/1.73m2

          -  Participants must have a performance status of 0-2 based on Eastern Cooperative
             Oncology Group (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

          -  Participants must sign the most current institutional review board (IRB)-approved
             study (informed consent form) ICF

        Exclusion Criteria:

          -  Prior autologous or allogeneic transplant

          -  Progressive disease on prior treatment

          -  Platelet count < 30 x 10^9/L, unless myeloma-related; if MM-related (hypercellular
             marrow biopsy of > 80% and packed with at least 80% plasma cells) the enrolling
             investigator must document this

          -  > Grade 3 neuropathy

          -  Known hypersensitivity to bortezomib, boron, or mannitol

          -  Uncontrolled diabetes on appropriate therapy

          -  Recent (=< 6 months) myocardial infarction, unstable angina, difficult to control
             congestive heart failure, uncontrolled hypertension on appropriate therapy, or
             difficult-to-control cardiac arrhythmias

          -  Participants must not have a creatinine >3 mg/dl or a GFR <30mL/min/1.73m2.

          -  Participants must not have a concurrent malignancy unless it can be adequately treated
             by non-chemotherapeutic intervention; participants may have a history of prior
             malignancy, provided that he/she has not had any chemotherapy within 365 days of study
             entry AND that life expectancy exceeds 5 years at the time of study entry

          -  Participants must not have life-threatening co-morbidities