Low-Risk Multiple Myeloma

2013-13 Total Therapy 4B: A Phase III Trial for Low-Risk Myeloma Ages 65 and Under: A Trial Enrolling Subjects to Standard Total Therapy 3 (S-TTS) Therapy

Principal Investigator: Dr. Barlogie

Primary Objectives:

Improve the therapeutic index of standard TT3 (S-TTS);

Conduct post, low-dose Melphalan Gene Expression Profiling (GEP) analysis in order to help unravel Melphalan’s mechanism of action

Secondary Objectives:

Employ serial MRI and FDG PET scanning to determine whether time of onset and frequency of imaging-defined CR in S-TT3 are preserved or even enhanced, due to enhanced compliance;

Perform genomic and proteomic analyses on CD 138-purified myeloma cells and normal host cells procured from randomly sampled iliac crest bone marrow sites and from MRI-defined focal lesions from time of diagnosis to remission and on to relapse.

Eligibility:

Patients with newly diagnosed, active, low-risk myeloma requiring treatment; patients with a history of smoldering myeloma if there is evidence of progressive disease requiring chemotherapy


 2008-03 Total Therapy 6: Phase II Trial for Patients Not Qualifying for TT4 and TT5 Protocols Because of Prior Therapy (No Prior Transplant)

Principal Investigator: Dr. Barlogie

Primary Objective:

To determine the rate of complete and near-complete response at two years after initiation of therapy

Secondary objectives:

To determine the frequency and duration of continued complete and near-complete response in relationship to: Duration of prior therapy (<6 months versus 6-12 months);.Prior response; Type of initial therapy, such as regimens containing Velcade or immunomodulatory agents (thalidomide, Revlimid) with or without melphalan

To determine duration of complete response and near-complete response

To determine event-free survival and overall survival

Translational research:

To apply separately bortezomib and low-dose Melphalan 10 mg/m2 and examine, via serial gene expression profiling (GEP) examinations of CD138-purified MM plasma cells (PC) and of un-separated bone marrow biopsy (BX) samples, whether “response” and “resistance” GEP signatures can be identified via short-term GEP alterations in PC and BX, analogous to observations in TT3 with Velcade

A sub-aim examines whether melphalan-induced changes are tumor cell specific or might be genetically predetermined; toward this aim, we will compare and contrast GEP in peripheral blood mononuclear cells and myeloma tumor cells prior to and following drug dosing


 2013-07 A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral MLN9708 Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma

Principle Investigator: Dr. Yogesh Jethava

Primary Objective:

To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves progression-free survival (PFS) in patients with newly-diagnosed multiple myeloma

(NDMM)

Key Secondary Objectives:

To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves the rate of complete response (CR)

To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves overall survival (OS)

To determine whether the addition of oral MLN9708 to lenalidomide and dexamethasone improves pain response rate, as assessed by the Brief Pain Inventory – Short Form (BPI-SF) and analgesic use

Eligibility:

Adult patients with a confirmed diagnosis of symptomatic MM, who have not received previous anti-myeloma treatment, who are not transplant eligible, and who are candidates for treatment with LenDex will be enrolled in this study.