Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

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

Precancerous Conditions

Hypergammaglobulinemia

All Drugs and Chemicals

Monatide (IMS 3015)

PD-L1 peptide (100 micrograms) emulsified with the adjuvant Montanide ISA-51 given subcutaneously 10 times every second week over the course of 26 weeks including a five-week break.

PD-L1 peptide

Nicolai Jørgensen, MD

This study is evaluating a new vaccine against PD-L1 as a possible treatment for high-risk smoldering multiple myeloma.

Smoldering multiple myeloma is an asymptomatic disorder with an annual risk of 10% of progression to the incurable cancer multiple myeloma. While many patients live for many years without progression, high risk patients have a median risk of progression of 29 months. No therapy has been approved for this indication. New treatments with limited adverse events are in high demand for this unmet medical need. An effective peptide vaccine would represent an ideal candidate, since vaccines generally have very low levels of side effects.

This study will explore if vaccination against the immune checkpoint molecule PD-L1 leads to responses in patients with high risk smoldering myeloma. PD-L1 is thought to play a role in the rate of progression from smoldering myeloma to symptomatic myeloma. Targeting this pathway with little risk of adverse events would potentially prevent or delay progression to symptomatic myeloma.

PD-L1 Peptide Vaccination in High Risk Smoldering Multiple Myeloma

Phase IIa Trial of PD-L1 Peptide Vaccination as Monotherapy in High Risk Smoldering Multiple Myeloma

measured by change in European Organization for Research and Treatment of Cancer (EORTC) QLQ-30.

measured by change in EuroQoL 5D-5-Level (EQ-5D-5L).

measured by change in and Hospital Anxiety and Depression Scale (HADS).

Overall response rates (ORR) defined by IMWG criteria as PR+VGPR+CR+sCR during treatment and two weeks after end of treatment per patient.

Blood, skin biopsies and bone marrow samples will be assessed with ELISPOT assays for levels of immune response to the vaccine.

Safety analysis will be conducted using the Safety Population defined as any patient receiving one dose of study treatment. For toxicity reporting, all adverse events and laboratory abnormalities will be graded and analyzed using CTCAE version 4 as appropriate.

PFS from diagnosis is defined as the time from diagnosis to the disease progression or death from any cause. Patients who have not progressed or died are censored at the date last known progression-free. This will be compared with published progression rates.

Time from diagnosis of SMM to progression to symptomatic myeloma compared to historical controls. Progression is defined as biochemical or diagnostic progression in accordance with the 2014 IMWG criteria for diagnosis of multiple myeloma which includes the classic CRAB-criteria as well as: Clonal bone marrow plasma cell percentage ≥ 60%, Free light chain ratio ≥ 100 (Involved FLC level must be ≥ 100mg/L),\> 1 focal lesion on MRI studies (at least 5 mm in size)

OS from diagnosis is defined as the time from diagnosis to the death of the patient.

IO Biotech

Lene Meldgaard Knudsen

Head of Department, Department of Hematology

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Waldenstrom Macroglobulinemia

Leukemia

Leukemia, Lymphoid

Lymphatic Diseases

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Irene Ghobrial, MD

The purpose of this study is to obtain bone marrow and peripheral blood samples, along with clinical data from patients with Multiple Myeloma (MM), Waldenstrom's Macroglobulinemia (WM), Smoldering MM, and other lymphoplasmacytic lymphomas (LPL) including but not limited to MGUS and IgG or IgA LPL. These samples will become part of a tissue bank and will be used in ongoing studies to find out more about the causes and biology of MM, WM and LPL; to identify what factors result in normal cells becoming cancer; to determine how to improve treatment options; to study how the immune system identifies abnormal cells; and to evaluate the immune function in these diseases. The investigators will also study the tumor cells at the level of the participant's genes to develop treatment strategies as well as to better understand how biologic differences affect patient outcomes.

* Participants will be asked to complete a medical survey which includes demographics, diagnosis, and treatment history, medical history, lab results and symptoms experienced.
* Participants will then receive instructions for the tissue banking procedure, which involves donating bone marrow and blood samples. These will be collected only at times when necessary clinical bone marrow samples are obtained and will not require an extra visit to the doctor.
* The investigators are also requesting permission to collect medical information from the participant's record and link this information to the specimens so that we may better understand the participant's response to treatment. For samples obtained prior to beginning therapy, this information might allow us to develop new ways of predicting response to therapy. The investigators are also requesting permission to store samples of blood and bone marrow to establish a tissue bank for future research to these diseases. These samples will be de-identified; any of the participant's personal health information identifiers will be removed.
* The tumor sample may be obtained at diagnosis, during treatment and/or as the time of relapse. The timing of sample collection will coincide with other bone marrow tests required to assess the response to therapy or any other clinical purpose.

Questionnaire and Tissue Banking For Multiple Myeloma, Waldenstrom Macroglobulinemia and Related Disorders

Medical Questionnaire and Tissue Banking For Multiple Myeloma, Waldenstrom Macroglobulinemia and Related Disorders

To establish a databank of patients with MM, WM, MGUS, sMM, or related disorders. This databank will include medical history data and bone marrow and peripheral blood samples.

To determine whether patients with MM, WM, MGUS, sMM, or related disorders have unique proteomic, genetic and epigenetic characteristics in the malignant clone or the microenvironment and linking information to the clinical characteristics of the patients through exploratory tests.

Dana-Farber Cancer Institute

Principal Investigator

Amino Acids

Tyrosine Kinase Inhibitors

Ibrutinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis

Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.

Ajai Chari, MD

The purpose of this research study is to test whether the drug ibrutinib (trademark name: IMBRUVICA®) is effective at preventing the development of multiple myeloma in people who currently have smoldering myeloma. The researchers conducting this trial) have reason to believe that ibrutinib can delay the development of multiple myeloma, thus giving people who currently have smoldering myeloma a longer period of time when they feel healthy and well.

Smoldering myeloma is an abnormal condition that is considered to be an early phase of the disease multiple myeloma. In this disorder, there is an abnormal growth of plasma cells, which is a type of blood cell found in the bone marrow. This growth is not as severe in people with smoldering myeloma as it is in multiple myeloma, so people with smoldering myeloma do not have any symptoms and tend to feel well. However, they have a higher risk of developing multiple myeloma than people in the general population.

Some people with smoldering myeloma are at an especially high risk of developing myeloma - 50% of these people will develop multiple myeloma 2 years after they are diagnosed with smoldering myeloma. The investigators identify these people by looking at the amount of myeloma in the bone marrow (called "bone marrow plasma cell percentage") and the amount of myeloma protein (called "serum protein electrophoresis" and "serum free light chain assay") in the blood. To be considered high risk, individuals must have highly abnormal levels for these tests.

Based upon current guidelines, people with smoldering myeloma do not require any treatment. However, known is that many of these people will develop multiple myeloma in the near future. Currently there have been no proven and effective way of preventing these people from developing multiple myeloma, which remains an incurable disease.

This is a phase 2, open-label, single center, prospective pilot study designed to assess the efficacy of ibrutinib in subjects with high risk smoldering multiple myeloma.

All enrolled subjects will be treated with ibrutinib 560 mg (4 capsules, each containing 140 mg) taken PO daily for 12 cycles (28 days each). If a subject demonstrates benefit from ibrutinib, therapy may be extended beyond 12 cycles to a maximum of 2 years. Subjects who progress and meet criteria for symptomatic multiple myeloma will be withdrawn from study.

An initial cohort of 15 subjects will be accrued. If 4 or more patients progress to symptomatic myeloma in one year, then the study will be reviewed with the FDA to determine whether to employ a higher dose of ibrutinib, or to stop for futility. Otherwise, 21 additional patients will be accrued for a total sample size of 36.

Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients

A Phase 2 Study of the Effect of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib on Disease Response in Patients With High Risk Smoldering Multiple Myeloma

Disease response - the proportion of patients with high risk smoldering multiple myeloma who do not progress to symptomatic myeloma as defined by the IMWG.

Overall response rate, defined as partial response or better per IMWG criteria. (IMWG response criteria are - Complete Response, Very good partial response, partial response, Minimal response, stable disease, and progressive disease)

Changes in bone density, particularly in patients with osteopenia (defined as T-score on bone densitometry testing (DEXA) of -1 to -2.5).

Changes in PET-MRI, particularly in patients with osteopenia

Pharmacyclics LLC.

Icahn School of Medicine at Mount Sinai

Associate Professor

Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis

Ibrutinib: Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.

50-59 years old

60 years and older

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Ajai Chari

Number of Patients Without Symptomatic Myeloma

Overall Response Rate

Bone Density Changes

PET-MRI Changes

Change in Serum Interleukin-6 (IL-6)

Change in Serum Stromal Cell-derived Factor-1 (SDF-1)

Change in Serum Receptor Activator of Nuclear-factor Kappa B Ligand (RANKL)

Change in Serum Macrophage Inflammatory Protein-1α (MIP-1α)

Change in Serum Dickkopf-1 (DKK-1)

Change in Serum C-terminal Telopeptide (CTX)

Change in Urine N-terminal Telopeptide (NTx)

Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose taken PO daily for 12 cycles (28 days each).

Ibrutinib: Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.

Overall Study

Behaviors and Mental Disorders

Aggression

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Lenalidomide

Daratumumab

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Non-high dose treatment in 3 phases Induction 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Consolidation 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Maintenance 12 cycles: lenalidomide, daratumumab

56 mg/m2 IV given on days 1, 8, and 15 of each cycle during induction and consolidation phases of the study.

Carfilzomib

25 mg po given on days 1-21 of each cycle during the induction and consolidation phases.

10 mg po given on days 1-21 of each cycle during the maintenance phase.

16 mg/kg IV given on days 1, 8, 15, and 22 of cycles 1-2; days 1 and 15 of cycles 3-6; day 1 of cycle 7-12; Day 1 of odd cycles for cycles 13-24.

40 mg oral given on days 1, 8, 15, and 22 of cycles 1-6 20 mg oral given on days 1, 8, 15, and 22 of cycles 7-12

Shaji Kumar, MD

Brian Durie, MD

This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each cycle is 28 days.

This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains incurable with the current approaches. The typical natural history of myeloma is one of repeated relapses, accompanied by genetic evolution and development of new abnormalities, which are often responsible for drug resistance. The presence of a precursor phase of smoldering myeloma, and the ability to identify those at the highest risk of progression, sets the stage to examine the possibility that we can cure the disease through early intervention. In order to potentially achieve this, we need to develop a highly effective combination that includes the most active drugs from different classes. Carfilzomib in combination with lenalidomide and dexamethasone results in high response rates and deep responses in subjects with newly diagnosed myeloma. Daratumumab in combination with lenalidomide results in high response rates in relapsed refractory disease. All these drugs are well tolerated and subjects are able to stay on them long term as a maintenance treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone presents the potential to enhance the effectiveness of the regimens. We hypothesize that this combination will lead to deep response including a higher proportion of minimal residual disease (MRD) negative disease among those with high risk smoldering myeloma and may translate into cure or long term disease quiescence.

Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles).

Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant

Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation, and Maintenance in Subjects With High Risk Smoldering Multiple Myeloma (SMM)

A confirmed sCR on 2 consecutive evaluations at any time during the course of treatment.

MRD negativity after induction, consolidation, and maintenance

Persistent MRD negativity rate will be evaluated at 1 year after completion of planned treatment consisting of induction, consolidation, and maintenance.

time of registration to death due to any cause

the time from registration to the earliest date of documentation of disease progression or death due to any cause

all eligible subjects that have initiated treatment will be considered evaluable for assessing adverse even rates. The maximum grade for each type of adverse event will be recorded. Relationship to trial treatment will be taken into consideration.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PD-L1 Peptide Vaccination in High Risk Smoldering Multiple Myeloma	NCT03850522	Smoldering Mult...	PD-L1 peptide	18 Years -	Herlev Hospital
Questionnaire and Tissue Banking For Multiple Myeloma, Waldenstrom Macroglobulinemia and Related Disorders	NCT01177527	Multiple Myelom... Waldenstrom's M... Smoldering Mult... Lymphoblastic L...		18 Years -	Dana-Farber Cancer Institute
Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients	NCT02943473	High Risk Smold...	Ibrutinib	18 Years -	Icahn School of Medicine at Mount Sinai
Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant	NCT03289299	Smoldering Mult...	Carfilzomib Lenalidomide Daratumumab Dexamethasone	18 Years -	International Myeloma Foundation
Questionnaire and Tissue Banking For Multiple Myeloma, Waldenstrom Macroglobulinemia and Related Disorders	NCT01177527	Multiple Myelom... Waldenstrom's M... Smoldering Mult... Lymphoblastic L...		18 Years -	Dana-Farber Cancer Institute
PD-L1 Peptide Vaccination in High Risk Smoldering Multiple Myeloma	NCT03850522	Smoldering Mult...	PD-L1 peptide	18 Years -	Herlev Hospital
PD-L1 Peptide Vaccination in High Risk Smoldering Multiple Myeloma	NCT03850522	Smoldering Mult...	PD-L1 peptide	18 Years -	Herlev Hospital

Spots Global Cancer Trial Database for smoldering

Every month we try and update this database with for smoldering 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 smoldering

Every month we try and update this database with for smoldering 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 smoldering 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.