Multiple Myeloma Clinical Trials and Research - University of Arkansas Medical Sciences

A hallmark of the Myeloma Institute for Research and Therapy (MIRT) is a program of clinical trials that challenge the traditional body of thought on disease treatment in order to improve outcomes. The physicians at MIRT work in tandem with myeloma scientists to bring the "bench of research to the bedside of the patient" and back again to optimize diagnosis and treatments.

The "Total Therapy" approach to the treatment of multiple myeloma, with its focus on attacking myeloma from all fronts, has been at the core of successful outcomes at MIRT. Starting with Total Therapy 1 in 1989, outcomes have continued to improve through the incorporation of new agents and adjustments in pre-transplant consolidation and post-transplant maintenance phases of care.

MIRT partners with SWOG (formerly the Southwest Oncology Group) on collaborative, multi-center clinical trials, and also participates in pharmaceutical industry trials in order to give patients access to some of the latest pharmaceutical advances.

To learn more about clinical trials, please visit the National Cancer Institute.

Clinical trials open to enrollment at MIRT:

2009-09

Myeloma Cure Project: Prospective, Randomized Trial of Indefinite Revlimid® Maintenance versus Observation for Currently Event-Free Patients with Multiple Myeloma (MM) Who Have Completed 3 Years of VTD/TD or VTD or VRD Maintenance on Total Therapy 3 (TT3) Trials 2003-33 and 2006-66

Principal Investigator: Dr. Barlogie

Primary Objective:

To determine, in a phase III trial, whether further maintenance therapy with Revlimid (REV, 10 mg/d) can extend the duration of progression-free survival (PFS) and the duration of complete or near-complete response (CR, n-CR) compared to no further therapy (NFT) beyond the TT3 protocol-prescribed 3 years of maintenance with 1 year of VTD plus 2 years with TD (n=276), 3 years with VTD (2003-33) or 3 years with VRD (2006-66).

Secondary Objectives:

To determine the associated toxicities in qualitative and quantitative terms using NCI CTCAE, Version 4.0 associated with REV versus NFT, related to REV and NFT dosing and duration of such therapies, in the context of pre-treatment parameters, especially in terms of platelet count and peripheral neuropathy
To determine whether the development of TT3-associated myelodysplasia (MDS)-associated CA can be favorably affected by REV v NFT, since REV has been shown to induce responses in de novo MDS

Eligibility:

Patients previously treated on TT3 without progression or relapse for 3 years continuously

2008-01

Total Therapy 4: A Phase III Trial for Low-Risk Myeloma; a Randomized Trial Comparing Standard Total Therapy 3 (S-TT3) with TT3-LITE (L-TT3)

Principal Investigator: Dr. Waheed

Primary Objectives:

Improve the clinical outcomes of patients with high-risk myeloma
Accelerate and sustain complete remission by reducing host-imposed toxicity

Secondary Objectives:

Perform gene expression profiling (GEP) of CD 138-purified myeloma plasma cells and of bone marrow biopsy samples, and determine whether “response” and “resistance GEP signatures can be identified
Discern the fundamental differences in myeloma and the host micro-environment inherent in focal lesions versus diffuse myeloma growth and thus potentially define a “dormant” myeloma stem-cell-like, non-secretory tumor compartment that may be key to treatment failure and disease recurrence
Provide a better understanding of a preferential myeloma sub-population cell kill as a means to distinguish whether relapse originates from the outgrowth of a minor resistant tumor sub-population or is due to further transformation during therapy
Validate and extend molecular classification and risk stratification models
Identify protein-based risk stratification models
Identify cell surface proteins on myeloma cells for the purpose of identifying potential new antibody-based therapeutic targets
Identify recurrent molecular changes related to relapse
Evaluate drug-induced effects on gene expression signatures in MM cells at diagnosis versus relapsed disease

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

2008-02

Total Therapy 5: A Phase II Trial for High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission (AS-CR) by Applying Non-Host-Exhausting and timely Does-Reduced Mel-80-VRD-PACE Tandem Transplants with Interspersed Mel-20-PACE and Alternating VRD and VMD Maintenance

Principal Investigator: Dr. Usmani

Objective:

Toward improving clinical outcomes of patients with high-risk myeloma in the context of earlier Total Therapy 3 trials, Total Therapy 5 is designed to accelerate and sustain at two years from starting therapy the proportion of patients in complete remission. This will be accomplished by reducing host-imposed toxicity and thus facilitating timely completion of highly synergistic 8-drug combination therapy, with the goal of avoiding myeloma regrowth.

Eligibility:

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

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:

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

2012-08

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 Relapsed and/or Refractory Multiple Myeloma

Principal Investigator: Dr. Usmani

Primary Objective:

To determine whether the addition of oral MLN9708 to the background therapy of lenalidomide and dexamethasone improves progression-free survival (PFS) in patients with relapsed and/or refractory multiple myeloma (RRMM)

Secondary Objectives:

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 OS in high-risk patients carrying deletion del(17)

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

2011-61

A Prospective Observational Study of Patients with Monoclonal Gammopathy (MGUS) and Asymptomatic Multiple Myeloma (AMM)

Principal Investigator: Dr. Waheed

Objectives:

To establish a serum, cell and tissue bank of prospectively collected samples from patients with MGUS, asymptomatic multiple myeloma, and other closely related disorders
To assess the feasibility of accruing patients with this disease
To assess the feasibility of accruing patients with this disease
To evaluate if patterns of gene expression or cytogenetics exist that allow molecular delineation of "MGUS subtypes"
To study DNA/CIg content by flow cytometry of these patients to identify aneuploidy patterns

2011-07

Phase 1/2 Open-Label, Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of SNS01-T Administered by Intravenous Infusion in Patients with Relapsed or Refractory Multiple Myeloma, Mantle Cell Lymphoma, or Diffuse Large B Cell Lymphoma

Principal Investigator: Dr. Usmani

Primary objective:

To evaluate the safety and tolerability of multiple escalating doses of SNS01-T when administered by intravenous infusion to patients with relapsed or refractory multiple myeloma, MCL, or DLBCL by assessing the frequency, severity, and duration of treatment-related adverse events (AEs) and monitoring changes in vital signs, physical examination, and laboratory values

Secondary objectives:

To characterize the pharmacokinetic profile of multiple doses of SNS01-T administered intravenously to patients with relapsed or refractory multiple myeloma, MCL or DLBCL by measuring pExp5A plasmid DNA and eIF5A siRNA in blood and bone marrow
To assess the potential immunogenicity of SNS01-T administered intravenously to patients with relapsed or refractory multiple myeloma, MCL or DLBCL by measuring serum concentrations of antibodies against SNS01-T nanoparticles
To measure the serum concentrations of select proinflammatory cytokines
To determine the effect of SNS01-T on time to relapse or progression To determine the effect of SNS01-T on tumor response in multiple myeloma using the International Myeloma Working Group (IMWG) uniform response criteria by analyzing the following:

Changes in serum and urine values of monoclonal protein (M-protein), immunoglobulin (Ig) kappa and lambda free light chain (FLC) and ratio, β2-microglobulin, lactate dehydrogenase, hemoglobin, and C-reactive protein
Changes in bone marrow plasma cell percentage and plasma cell labeling index

To determine the preliminary response of SNS01-T in MCL and DLBCL using the Revised Response Criteria for Malignant Lymphoma, and by assessing changes in appropriate signs, symptoms and lab results

2012-12

Therapeutic Research in Multiple Myeloma and Related Disorders

Principal Investigator: Dr. Barlogie

Objective:

To understand the biology of multiple myeloma and related disorders and thereby effectuate growth control of myeloma tumor cells

Eligibility:

Newly Referred patients, no prior therapy AND previously treated patients

2009-88

Collection of Bone Marrow for Molecular Genetics Studies

Principal Investigator: Dr. Barlogie

Objectives:

To support Myeloma Institute research investigations by providing genomic and proteomic profiling of clinical material and cells from healthy volunteer donors
To serve as a source of human biological samples and corresponding laboratory and clinical data for myeloma-related research

Eligibility:

Healthy donors without diagnosis of multiple myeloma

2003-15

Protocol for a Research Sample Repository for Allogeneic Hematopoietic Stem Cell Transplantation

This supports an International Data Repository for many cancer types. The Myeloma Institute provides data only.

Principal Investigator: Dr. van Rhee

The National Marrow Donor Program (NMDP) / Center for International Blood and Marrow Transplant Research (CIBMTR) is trying to learn more about what makes bone marrow, blood stem cell and cord blood transplants work well. Although the exact studies for which Research Repository samples may be used is not known at this time, the types of studies in which these data may be included are designed to:

Improve the understanding of tissue matching for related and unrelated donors and recipients
Determine and evaluate the factors that affect transplant outcome
Study the distribution of tissue types in different populations; e.g., study tissue typing differences between different racial and ethnic populations to help develop methods that will improve tissue matching between donors and recipients
In addition, it is possible that investigators may conduct research studies with stored blood samples that have had all identifiers removed. In these studies, there will be no way for the sample to be linked to the patient. NMDP/CIBMTR may allow investigators to use these anonymous samples for many other kinds of studies. These studies are not limited to the types of studies listed above, or related to transplantation in general.

2003-16

Protocol for a Research Sample Repository for Hematopoietic Stem Cell Transplantation, Other Cellular therapies and Marrow Toxic Injuries

This supports an International Data Repository for many cancer types. The Myeloma Institute provides data only.

Principal Investigator: Dr. van Rhee

Objectives:

The National Marrow Donor Program (NMDP) / Center for International Blood and Marrow Transplant Research (CIBMTR) is trying to learn more about what makes bone marrow, peripheral blood stem cell and cord blood transplants and other cellular therapies work well. Although the exact studies for which Research Database data may be used is not known at this time, the types of studies in which these data may be included are designed to:

Determine how well recipients recover from their transplant or cellular therapy
Determine how recovery after a transplant or cellular therapy can be improved
Determine how access to transplant or cellular therapy for different groups of patients can be improved
Determine how well donors recover from the collection procedures

Eligibility:

Any recipient of an unrelated or related donor or autologous HC transplant (includes cells collected from peripheral blood, bone marrow or cord blood) in a CIBMTR center is eligible to participate in the Research Database.