Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Nutritional and Metabolic Diseases

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Smoldering Multiple Myeloma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Proteostasis Deficiencies

Metabolic Diseases

Precancerous Conditions

Hypergammaglobulinemia

AL Amyloidosis

Raymond Comenzo, MD

Denis Toskic, BS

Susan Bal, MD

Robert Vescio, MD

Lisa Lee, MD

Tom Martin, MD

Chakra Chaulagain, MD

Giada Bianchi, MD

Suzanne Lentzsch, MD

Heather Landau, MD

Cindy Varga, MD

Sascha Tuchman, MD

Gurbakhash Kaur, MD

Amandeep Godara, MD

Hashim Mann, MD

In this multicenter study, we will recruit 400 patients 40 years of age or older at 15 centers with a diagnosis of smoldering multiple myeloma (SMM), a group of patients for whom standard of care is observation not treatment. The main goal of this study is to screen for the diagnosis of light-chain amyloidosis (AL) before the onset of symptomatic disease and to develop a training set for a likelihood algorithm.

This study is based on results from two prior studies in which 4 of 36 patients with SMM and none of 14 patients with MGUS were found to have AL. The hypothesis that we test with this protocol is that patients with (1) a pre-existing diagnosis of SMM, (2) free light chain (FLC) abnormalities, (3) IGLV genes associated with AL,(4) t(11;14) or gain 1q, and (5) NT-proBNP \> 332pg/mL will have undiagnosed AL or risk of progression to AL. We will study the potential for SMM, the FLC screen, AL-related IGLV gene use, t(11;14) or gain 1q cytogenetic abnormalities, and NT-proBNP \> 332pg/mL to be the variables in a likelihood algorithm for AL.

cDNA derived from bone marrow CD138-selected plasma cells.

Screening for AL Amyloidosis in Smoldering Multiple Myeloma

With a 15-center network covering 12 states and almost 45% of the US population, we will evaluate 400 SMM patients \> 40 years old who pass FLC criteria using standard of care tests including NT-proBNP and clinical marrow specimens evaluated for the presence of t(11;14) and gain1q. Marrow cells will be processed by NGS for clonal IGLV gene identification. With the training data obtained, we will use existing statistical modeling techniques to generate a statistical algorithm for identifying undiagnosed cases of AL and assessment of risk of AL, and to plan a validation study testing the training model. We will also investigate a role for the novel biomarker clusterin (Clu) as an indicator of risk of AL in SMM patients; preliminary work indicates that Clu is significantly lower in AL than in SMM patients.

All subjects will have their clonal IGLV genes identified by NGS enabling the creation and validation of a laboratory developed test in a precision medicine laboratory that is certified under regulations of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Approval for this laboratory developed test for both κ and λ IGVL genes will permit providers, patients and researchers to use the test in decision-making to care for monoclonal gammopathy patients. We will also investigate the exploratory objective of defining the alterations in sequence in AL and non-AL FLC derived from the same IGLV germline gene.

National Cancer Institute (NCI)

Tufts Medical Center

Monoclonal Gammopathy of Undetermined Significance

The purpose of this study is to see whether certain genes may be linked with the development of AL amyloidosis in subjects 60 years of age or older with the blood disorders SMM and MGUS. A limited repertoire of immunoglobulin (Ig) variable region genes have been associated with AL amyloidosis. The clonal plasma cells of subjects with SMM and MGUS may express one of these Ig variable region genes indicating a risk of progression to AL amyloidosis and potentially enabling early diagnosis. We hope this study will help us begin to understand whether Ig variable region gene identification can be a useful tool for assessing a subject's risk of progression to AL amyloidosis.

Screening to Improve Survival in AL Amyloidosis

By creating a multicenter network (N =6) we will have study centers in Massachusetts (1), California (2), New York (1), North Carolina (1) and Florida (1), enabling us to evaluate 50 patients 60 or older with λ SMM or λ MGUS and to determine based on gene identification whether their clonal λ IGVL genes are AL-related. This approach will identify undiagnosed patients early in the course of AL and patients at risk for AL.

Testing for markers such as λ IGVL germline genes is highly complex as defined by the Clinical Laboratory Improvement Act (CLIA) (42 USC 263a). We will continue identifying clonal λ IGVL genes with RT-PCR using cDNA derived from bone marrow CD138-selected plasma cells in our research lab, and have partnered with a CLIA-certified diagnostic laboratory, the Columbia University Laboratory of Personalized Genomic Medicine, in order to develop and validate a next generation sequencing (NGS) approach as a CLIA compliant B-cell Gene Rearrangement Test (BCGR, CPT: 81261).

The multicenter trial will employ bone marrow aspirate mononuclear cells in two ways. First, a portion of each patient's marrow mononuclear cells will be used directly for cDNA for NGS and a portion used to select CD138+ plasma cells for cDNA for RT-PCR and NGS. The use of cDNA derived from bone marrow aspirate mononuclear cells for NGS would save the step of selection and be more convenient if it is equally informative. Criteria identifying specimens that likely do or do not require CD138-selection may be identified in this process.

National Institute on Aging (NIA)

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Disease Progression

Lymphatic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Other Dietary Supplements

All Drugs and Chemicals

Omega 3 Fatty Acid

Omega 3 supplement will be added to diet, 3 capsules per day for one month then 6 capsules per day for one month then 9 capsules per day as tolerated

Omega 3 supplementation will be initiated at three 1250 mg capsules daily for the first month. If dose is well tolerated, it will be increased to six 1250 mg capsules daily for 30 days, and finally to nine 1250 mg capsules daily. Treatment period is 12 months.

Wanda E Hardman, Ph.D.

Escalating doses of Omega 3 Fatty Acids are being used in patients who have early stage Chronic Lymphocytic Leukemia (ES-CLL), Monoclonal Gammopathy of Undetermined Significance (MGUS), or Smoldering Multiple Myeloma (SMM), whose disease does not currently require treatment. The primary aim of the study is to determine if the Omega 3 supplementation will help prevent or delay progression of the disease to a stage that requires treatment.

Prevention of Disease Progression in Early Stage Indolent B Cell Malignancies. (SMM)

Inhibition of Nuclear Factor Kappa B for Prevention of Disease Progression in Indolent B Cell Malignancies

Peripheral lymphocytes were isolated from the blood using Ficoll-Paque gradient. Nuclear Factor Kappa B activation was analyzed using Thermo Scientific Transcription Factor kit for NFkB p50, according to manufacturer's protocol. Protein extracts containing 1-15µg of protein/well were added in triplicates. Luminescence resulting from a reaction with bound NFkB was detected using a Berthold Centro LB960 Luminometer and analyzed with MikroWin 2000 ver. 1.08. NFkB activity was normalized by luminescence units/µg of protein per well.

Patients diagnosed with early stage (asymptomatic) CLL were supplemented with escalating doses of omega-3 (n-3) fatty acids (2.4 g of n-3/day up to 7.2 g of n-3/day). Given that these patients are asymptomatic and did not require treatment, measures of tumor mass during and after omega-3 supplementation, as evaluated by standard clinical tests of disease activity, were not performed. Instead, absolute lymphocyte counts (ALC), as a measure of tumor burden, was evaluated before and after omega-3 supplementation. Data represents the fold change in ALC post omega-3 consumption as compared to baseline ALC.

Patients with MGUS or SMM were not enrolled into this study.

Edwards Foundation, Inc.

Marshall University

W. Elaine Hardman, Ph.D., Marshall University School of Medicine, Professor of Biochemistry and Microbiology

Serious adverse effects associated with omega 3 fatty acid consumption.

Adverse Effects

Omega 3 Supplementation

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. W. Elaine Hardman

Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.

Analysis based on global response.

Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.

Analysis based on High Initial NFkB Activation Expressers.

Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α\< 0.05.

Analysis based on Low Initial NFkB Activation Expressers.

Total Population

Higher Initial Expressers

Lower Initial Expressers

Baseline nuclear factor Kappa B (NFkB) activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia.

Baseline Nuclear Factor Kappa B Activation

Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following consumption of 3 capsules per day (2.4 g of omega 3 per day). Each 1250mg capsule provided 800mg of omega 3.

Nuclear Factor Kappa B Activation Following 3 Capsules Per Day

Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following consumption of 6 capsules per day (4.8 g of omega 3 per day).Each 1250mg capsule provided 800mg of omega 3.

Nuclear Factor Kappa B Activation Following 6 Capsules Per Day

Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following consumption of 9 capsules per day (7.2 g of omega 3 per day). Each 1250mg capsule provided 800mg of omega 3.

Nuclear Factor Kappa B Activation Following 9 Capsules Per Day

Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following discontinued consumption of omega 3.

Nuclear Factor Kappa B Activation Post Supplement

NFkB activation of all patients diagnosed with early stage CLL at baseline and following omega 3 consumption. Patients are further separated into high (\> median, n=7) and low initial baseline (\< median, n=6) NFkB. Patients included must have had one baseline and at least one period of omega 3 consumption. Not all patients completed all periods

Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement.

Fold change in ALC after omega-3 consumption as compared to baseline ALC.

Fold Change in ALC-Patient 1

Fold Change in ALC-Patient 2

Fold Change in ALC-Patient 3

Fold Change in ALC-Patient 4

Fold Change in ALC-Patient 5

Fold Change in ALC-Patient 6

Fold Change in ALC-Patient 7

Fold Change in ALC-Patient 8

Fold Change in ALC-Patient 9

Fold Change in ALC-Patient 10

Fold Change in ALC-Patient 11

Fold Change in ALC-Patient 13

Fold Change in ALC-Patient 14

Patients who's absolute lymphocyte counts were known prior to omega-3 initiation (baseline) and after omega-3 consumption were included in this analysis. Patients who's ALC was unknown prior to omega-3 initiation or after omega-3 consumption were excluded.

The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity.

Baseline blood specimens were obtained. All participants were then assigned to consume three, 1250mg omega 3 supplement capsules per day (providing 2.4g of omega 3 total) for one month, the first period. Blood was obtained and participants were assigned to consume six, 1250mg capsules of omega 3 per day (providing 4.8g of omega 3)for one month, the second period. Blood was again obtained and participants were assigned to consume 9 capsules of omega 3 per day, providing 7.2g of omega 3,the third period.

Overall Study

Patients with Monoclonal gammopathy of undetermined significance or smoldering myeloma

Gene expression profiling, DNA copy number variation

Genetic study of DNA copies

Olivier DECAUX, MD

The purpose of this study is to describe DNA copy number variations and gene expression profiles of bone marrow plasma cells of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). The final objective is to search for correlations with the risk of progression in order to establish a predictive model of early malignant transformation.

Study of DNA Copy Numbers Variations and Gene Expression Profile of Bone Marrow Plasma Cells From MGUS and SMM.

Large Scale Study of DNA Copy Numbers Variations and Gene Expression Profile of Bone Marrow Plasma Cells From Monoclonal Gammopathy of Undetermined Significance (MGUS) and Indolent Myeloma (SMM).

Intergroupe Francophone du Myelome

Rennes University Hospital

Syndrome

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Hematologic Neoplasms

Bone Marrow Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Dermatologic Agents

Vaccines

Molgramostim

Sargramostim

Immunomodulating Agents

Monatide (IMS 3015)

Mineral Oil

Immunologic Factors

Adjuvants, Immunologic

BB-MPI-03 peptides plus montanide plus sargramostim

Drug: Sargramostim (GM-CSF) Other Names: Leukine Sargramostim (250 ug vial) is reconstituted with 0.5 ml of Sterile Water for Injection. Subjects will receive 0.5 ml intradermally (250 µg) near the arm pit or inside of thigh.

Other Names: Multi-peptide immunotherapy (MPI) is comprised of 3 cytotoxic T-cell epitopes derived from oncofetal antigen. There are 3 dose levels of study vaccine planned to be tested, starting at 0.25 mg each peptide (0.75 mg total peptide dose), then 0.5 mg of each peptide (1.5 mg total) and finally 1 mg each peptide (3 mg total). At the starting dose of 0.75 mg, the BB MPI 03-15 mg vial is used and 100 ul is administered; at the 1.5 mg dose, 200 ul of the BB MPI 03-15 mg vial is used; at the 3 mg dose, 200 ul of the BB MPI 03-30 mg is used.

BB-MPI-03

Drug: Montanide Other Names: mineral oil, USP BB-MPI-03 is emulsified with Montanide and administered intradermally (ID) within 1-2 cm of the 2 sargramostim injection sites 1-3 minutes after sargramostim administration.

Subjects and the injection sites are to be monitored for 1 hour after sargramostim and BB-MPI-03 emulsion administration.

Montanide

The study is designed to evaluate safety, immunogenicity, and preliminary anti-tumor activity of a multi-peptide immunotherapy (BB-MPI-03) at three peptide+adjuvant dose levels. The peptides stimulate cytotoxic T-cells targeting oncofetal antigen (OFA). Subjects with AML, MM, sMM, or MDS who are off treatment and with stable disease or better, or who are not eligible for or refuse allogeneic HSCT are to be enrolled. The study will be conducted at 2 to 4 study centers in the US.

The current study is a Phase I, open-label, multi-center, dose escalation study designed to evaluate safety, immunogencity, and potential anti-tumor activity of BB-MPI-03 at three peptide plus adjuvant dose levels. Subjects with acute myelogenous leukemia (AML), multiple myeloma (MM), smoldering multiple myeloma (sMM), or myelodysplastic syndrome (MDS) who are off treatment and with stable disease or better or who are not eligible for or refuse allogeneic hematopoietic stem cell transplantation (HSCT) are to be enrolled. The study will be conducted at 2 to 4 study centers in the United States (US).

The study employs a sequential group, open-label, 3+3 dose- escalation design to determine the safety and MTD of BB- MPI-03.

Phase I Study of an Oncofetal Antigen Multi-Peptide Immunotherapy in Subjects With Hematologic Cancer

Phase I Study of an Oncofetal Antigen ("OFA") Multi-Peptide Immunotherapy ("BBMPI03") in Subjects With Hematologic Cancer

The safety and tolerability of BB-MPI-03 in Montanide emulsion preceded by sargramostim will be measured by:

* The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), DLTs, and AEs leading to study vaccine discontinuation.
* The proportion of subjects requiring a modification of the study treatment dose or schedule.
* Change from baseline in absolute neutrophil counts (ANC) and platelet counts.
* The proportion of subjects with local injection site reactivity.
* Proportion of subjects experiencing infections or fevers requiring hospitalization and/or intravenous (IV) antibiotics.

Immunologic responses (change from Baseline) will be assessed by:

* DTH reaction to the peptides, as measured and photographed at 7 months using the "ballpoint pen" method.
* Peptide-specific T-cell proliferation to ELISPOT and tetramer assay.
* Level of OFA expression on tumor cells at Month 7.
* Anti-peptide (anti-OFA) antibodies in the serum. These parameters will be measured at D15, D29, M2, M3, M6, M9, and M12 and compared to pre-treatment Baseline. DTH reaction to the peptides and OFA expression will be measured and recorded at 1 month after the last injection (M7).

The anti-tumor activity of BB MPI 03 in Montanide emulsion preceded by sargramostim will be measured by:

Time to progression (TTP) Overall response rate at Month 7 Best Overall Response

Benovus Bio, Inc.

Plasmacytoma

patients with either Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM)

Mark J Roschewski, M.D.

Background:

- Multiple myeloma is a type of cancer that affects white blood cells and has a poor long-term survival rate. Two other types of cancer, monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), may eventually progress and develop into multiple myeloma. Researchers are interested in collecting samples from individuals who have been diagnosed with MGUS and SMM to study possible risk factors for developing multiple myeloma.

Objectives:

- To study risk factors that may cause MGUS and SMM to progress to multiple myeloma.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with either MGUS or SMM but do not have multiple myeloma.

Design:

* Participants will be examined by study researchers at the initial visit, at 6 months following enrollment, and every 12 months for a maximum of 5 years.
* The following tests may be performed: (1) blood and urine tests, (2) bone marrow aspiration and biopsy, (3) imaging studies, and (4) a skeletal survey (a series of skeletal X-rays of the skull, spine, pelvis, ribs, shoulders, upper arm, and thigh bones).
* Treatment will not be provided as part of this protocol. - Participants will remain on the study for 5 years, or until their MGUS or SMM progresses to multiple myeloma requiring treatment.

Background:

* Multiple Myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4 years.
* Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are premalignant plasma cell proliferative disorders characterized by elevated monoclonal protein and bone marrow plasma cells. MGUS affects 3.2% of Caucasians over the age of 50 and has a 1% annual risk of progression to MM. approximately 3000 cases of SMM are diagnosed annually with a 10% annual risk of progression to MM.
* Current risk stratification schemes rely on serum protein markers and phenotyping by flow cytometry. While they can differentiate high and low risk patients, they cannot predict outcome for individual patients, are not integrated with one another, and have limited direct correlation to biology.
* Paired samples linked to clinical information can advance research into improved risk stratification, the pathogenesis of MGUS, SMM, and MM, and the potential for an early treatment window for these incurable diseases.

Objectives:

* To characterize the natural history and prognosis of MGUS and SMM
* To integrate protein markers (including immunoglobulin free light-chains) and immunophenotyping by flow cytometry with molecular profiles (including gene expression profiles) and clinical outcomes
* To apply expertise and diagnostic technology to provide improved evaluation, monitoring, and risk-stratification for patients on this protocol
* To provide paired samples of blood and tissue linked to clinical and molecular information for pilot translational studies

Eligibility:

* A confirmed diagnosis of MGUS or SMM (based on IMWG diagnostic criteria)
* Age greater than or equal to 18 years
* ECOG performance status in the range of 0-2
* Patients who have a diagnosis of MM are not eligible for this study.

Design:

* This is a prospective cohort study of patients with either MGUS or SMM.
* Following initial evaluation and confirmation of diagnosis, patients will be followed as clinically indicated, usually at 12 month intervals.
* The primary endpoint is progression to MM requiring treatment.
* Patients may donate cellular products or tissues as appropriate for research purposes.

  154 patients with MGUS and 154 patients with SMM will be enrolled on this protocol.

Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM)

determination of subtypes of MM based on GEP, and determination of prognostic indicators

comparison of molecular profiles and rate of disease progression per MM subtype

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Screening for AL Amyloidosis in Smoldering Multiple Myeloma	NCT06365060	Smoldering Mult...		40 Years -	Tufts Medical Center
Screening to Improve Survival in AL Amyloidosis	NCT04615572	Smoldering Mult... Monoclonal Gamm...		60 Years -	Tufts Medical Center
Screening to Improve Survival in AL Amyloidosis	NCT04615572	Smoldering Mult... Monoclonal Gamm...		60 Years -	Tufts Medical Center
Prevention of Disease Progression in Early Stage Indolent B Cell Malignancies. (SMM)	NCT00899353	Monoclonal Gamm... Smoldering Mult... Chronic Lymphoc...	Omega 3 Fatty A...	18 Years -	Marshall University
Study of DNA Copy Numbers Variations and Gene Expression Profile of Bone Marrow Plasma Cells From MGUS and SMM.	NCT01079429	Monoclonal Gamm... Smoldering Myel...	Genetic study o...	18 Years - 70 Years	Rennes University Hospital
Screening to Improve Survival in AL Amyloidosis	NCT04615572	Smoldering Mult... Monoclonal Gamm...		60 Years -	Tufts Medical Center
Study of DNA Copy Numbers Variations and Gene Expression Profile of Bone Marrow Plasma Cells From MGUS and SMM.	NCT01079429	Monoclonal Gamm... Smoldering Myel...	Genetic study o...	18 Years - 70 Years	Rennes University Hospital
Phase I Study of an Oncofetal Antigen Multi-Peptide Immunotherapy in Subjects With Hematologic Cancer	NCT02240537	Acute Myelogeno... Multiple Myelom... Myelodysplastic... Smoldering Mult...	Sargramostim BB-MPI-03 Montanide	18 Years -	Benovus Bio, Inc.
Study of DNA Copy Numbers Variations and Gene Expression Profile of Bone Marrow Plasma Cells From MGUS and SMM.	NCT01079429	Monoclonal Gamm... Smoldering Myel...	Genetic study o...	18 Years - 70 Years	Rennes University Hospital
Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM)	NCT01109407	Smoldering Myel... Monoclonal Gamm...		18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for smm

Every month we try and update this database with for smm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for smm

Every month we try and update this database with for smm cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for smm cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.