Newly Diagnosed Multiple Myeloma

2012-02 Total Therapy 5B:  A Phase II Trial for High-risk Myeloma Evaluating Accelerating and Sustaining Complete Remission (AS-CR) By Applying Non-Host-Exhausting and Timely Dose-Reduced MEL-80-CFZ-TD-PACE Transplant(s) with Interspersed MEL-20-CFZ-TD-PACE with CFZ-RD and CFZ-D Maintenance

Principal Investigator: Dr. van Rhee

Primary Objectives:

TT5B will attempt to accelerate and sustain, at 2 years from starting therapy, the proportion of subjects in complete remission (AS-CR-2) by reducing host-imposed toxicity and thus facilitating timely completion of highly synergistic 8-drug combination therapy, including the next generation proteasome inhibitor, Carfilzomib (CFZ).  This will result in avoiding MM re-growth that, we postulate, ensued in TT3 during recovery phases from severe de-conditioning. Furthermore, we speculate that the incidence of positive minimal residual disease (MRD) will be reduced with the addition of one cycle of consolidation therapy. Toward this goal, the following approach will be implemented:

Secondary Objectives:

To perform, 48hr after CFZ 20 mg/m2 followed by 48 hour post melphalan 10 mg/m2, gene expression profiling (GEP) examinations of CD138-purified MM plasma cells (PC) and of bone marrow biopsy (BX) samples, and determine whether “response” and “resistance” GEP signatures can be identified via short-term GEP alterations in PC and BX, analogous to observations in TT3 with bortezomib1.

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

To perform such GEP examinations plus proteomic analyses on PC and BX procured from randomly sampled (RS) iliac crest bone marrow sites and from MRI-defined focal lesions (FL) under CT-guidance during defined phases of TT5B from the time of diagnosis to remission and on to relapse.

Eligibility:

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


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

Eligibility:

Newly diagnosed or previously treated, but with no prior transplant; no prior Thal or Rev severe toxicities; creatinine < 3mg/dL


SWOG 1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma

Principal Investigator: Dr. van Rhee

Primary Objectives:

Phase I

To determine appropriate Phase II dose of elotuzumab to use in combination with lenalidomide, bortezomib and dexamethasone for patients with multiple myeloma.

Phase II

To assess whether incorporation of the novel agent elotuzumab into the treatment algorithm of high risk multiple myeloma (HRMM) will improve progression-free survival (PFS).

To estimate the frequency and severity of toxicities of this treatment strategy in this patient population.

Eligibility:

Patients with newly diagnosed multiple myeloma; Phase II is designed for newly diagnosed high risk multiple myeloma patients.


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.