Previously Treated Multiple Myeloma

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


2010-35 A Phase II Study of Expanded Natural Killer Cell Therapy for Multiple Myeloma

Principal Investigator: Dr. van Rhee

Primary Objective:

To determine the therapeutic efficacy of the exp-NK cell therapy in research participants with relapsed high risk MM [defined as gene expression profile (GEP) 70 gene score ≥0.66 and/or GEP 80 gene score of ≥ 2.48 and/or metaphase chromosomal abnormalities and/or high LDH ≥ 360U/L] by establishing the (near) complete response rate. Response rate will be compared to case matched historical controls (patients who relapsed on Total Therapy 2 or 3 with high-risk MM defined as above). Disease-free survival and overall survival will be captured but are not primary or secondary endpoints.

Secondary Objectives:

To monitor the persistence of exp-NK cells by molecular methods in recipients of haploidentical exp-NK cells;

To determine whether escape from exp-NK cell recognition is the mechanism for relapse in those who fail the proposed therapy

Eligibility:

Patients with high-risk disease; Previously-treated patients; Relapsed/Refractory patients