View clinical trials related to Paraproteinemias.
Filter by:The goal of this observational study is to study the genetic landscape in patients with Plasma Cell Disorders including MGUS, SMM, MM, and amyloidosis in Thailand. The main questions it aims to answer are: - genetic landscape in patients with Plasma Cell Disorders including MGUS, SMM, MM, and amyloidosis in Thailand who were performed FISH and/or NGS testing - genetic correlation and genetic dependency between FISH and NGS, stratified by high- and standard-risk groups based on FISH testing in Thai MM patients. - disease characteristics and response rates in MM patients with cytogenetic abnormalities detected by FISH and/or genetic mutations detected by NGS. - correlation between cytogenetic abnormalities identified by FISH and genetic mutations detected by NGS with progression-free survival in MM patients. The FISH and/or NGS testing results, disease characteristics, treatment, and treatment outcomes of patients with plasma cell disorders who underwent FISH and/or NGS testing before IRB approval will be collected through retrospective chart review. Subsequently, data will be gathered prospectively. Participants will provide approximately 12 mL of bone marrow fluid for FISH and NGS testing.
The purpose of this research is to evaluate whether HDAA in combination with a single dose of 100 mg/m2 IV melphalan followed by autologous stem cell transplantation (ASCT) is safe and effective for subjects with relapsed refractory multiple myeloma. The proposed melphalan dose is 50% of the current standard myeloablative dose (200 mg/m2). Based on our preclinical data, the investigator hypothesize that the combination of reduced dose melphalan with IV HDAA will have high efficacy and tolerability Primary Objective To determine tumor response using International Myeloma Working Group (IMWG) criteria (see Appendix B). Secondary Objectives Objectives: 1. Determine the safety and tolerability of HDAA in combination with reduced dose melphalan conditioning and autologous stem cell transplantation (ASCT) in relapsed refractory multiple myeloma subjects. 2. Determine the rate of Minimal Residual Disease (MRD) negativity at time point of response assessment using 8 color flow cytometry on BM sample. Functional imaging, such as positron emission tomography (PET) scan and magnetic resonance imaging (MRI), will also be performed to assess the disease status. 3. Categorize and quantify adverse events compared to historical control. 4. Determine quality of life parameters using standardized health-related quality of life measures 5. Determine oxidative stress parameters in plasma during treatment.
The goal of this observational study is to register patients with plasma cell disorders. The main questions it aims to answer are: - The incidence of plasma cell disorders both before and after malignancy - Time to progression of monoclonal gammopathy of undetermined significant (MGUS) or smoldering multiple myeloma (SMM) to light chain amyloidosis or multiple myeloma (MM) - Progression free survival (PFS) - overall survival - factors influencing overall survival, progression-free survival, and time to progression - Symptoms and signs of the disease during the diagnosis and relapse phases, including the causes of mortality in plasma cell disorder patients. - genetic characteristics of plasma cell disorder - cost-effectiveness of treatment in Thailand Participants will be collected the data of baseline diagnosis, treatment, treatment results of all admission and follow-up visits from hospital medical record.
The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of high-risk monoclonal gammopathy of undetermined significance (HR-MGUS) and non high-risk smoldering multiple myeloma (NHR-SMM). This requires understanding the safety and tolerability of the study drug (how the body reacts to linvoseltamab) as well as the effectiveness of the study drug (how well linvoseltamab eliminates plasma cells). All participants will start treatment with gradually increasing doses of linvoseltamab (step-up doses) before they start receiving the assigned full dose. The study is split into 2 parts: - In Part 1, separate groups of 3-6 patients will receive different full doses of linvoseltamab to evaluate the short-term side effects (safety) and tolerability of the study drug within the first 5 weeks after starting treatment. The data collected will help to make a decision about the dosing regimens chosen for Part 2. - In Part 2, a larger number of participants will be randomized to different dosing regimens to further assess the side effects of linvoseltamab, and to evaluate the ability of linvoseltamab to eliminate abnormal plasma cells in HR-MGUS and NHR-SMM. The study is looking at several other research questions, including: - How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-SMM? - What side effects may happen from taking the study drug? - How much study drug is in the blood at different times? - Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects).
Ambispective, national, multicenter observational cohort study aimed at characterizing the satellite dysimmune manifestations of clonal hematopoiesis, including Vexas (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome.
The objective of this investigator-initiated phase II single-arm open-label clinical trial is to investigate neurological response rate, safety and tolerability of Zanubrutinib 320 mg daily in combination with Rituximab 375 mg/m2 (standard therapy) for the treatment of immunoglobulin M monoclonal gammopathy of unknown significance (IgM MGUS) related polyneuropathy with Myelin Associated Glycoprotein antibodies (anti-MAG). 42 adult patients will be included in two Dutch hospitals (University Medical Center Utrecht and Amsterdam University Medical Center). This trial consists of a 6-month treatment period, after which the hematological response will be evaluated. Adequately responding participants (at least partial response) will be treated for an additional 6 months, after which hematological response will be re-evaluated. Participants with at least a very good partial response will remain on treatment. Non-responding participants will be followed for clinical outcomes only. The total study period per participant will be 36 months.
This is a phase 1/2, open label, single-center study designed to assess the safety and preliminary clinical activity of different belantamab mafodotin doses in combination with daratumumab, pomalidomide, and dexamethasone (DPd) in patients with Relapsed/ Refractory Multiple Myeloma (RRMM) previously treated with one line of therapy who are lenalidomide refractory. This will be a 2-Part study. Part 1 will evaluate the safety of belantamab mafodotin in combination with DPd in 2 cohorts and determine the Recommended Phase 2 Dose (RP2D). In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 will further evaluate the safety and assess the preliminary clinical activity of the belantamab mafodotin RP2D in combination with DPd. Overall, approximately 48 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is randomized. The estimated accrual period will be 12 months corresponding to an approximate total study duration of 4 years.
This is an investigator-initiated (IIS), phase 2, prospective, open-label, multinational study, designed to be conducted in approximately 14 sites. Eligible patients will initially receive six 28-day cycles of isatuximab, pomalidomide, and low-dose dexamethasone. Following this phase: Patients who achieve ≥VGPR will be randomized in a 1:1 ratio to receive isatuximab, given either Q2W or once monthly, plus pomalidomide and low-dose dexamethasone. Patients with <VGPR will continue treatment with isatuximab Q2W, pomalidomide, and low-dose dexamethasone. The study will last for 42 months (recruitment and follow-up period), starting from the date of the first patient in (FPI) to the date of the last patient last visit (LPLV). Core study procedures consist of baseline and post-baseline safety and disease evaluations, including physical examination, hematologic/clinical chemistry tests, radiologic assessments, bone marrow evaluations, and blood/urine M-protein assessments. Patients will be allowed to continue treatment until disease progression, death, unacceptable AEs, lost to follow-up, or consent withdrawal.
This is an Investigator-Initiated, phase 2, prospective, open-label study designed to be conducted in six hospitals in Greece. Eligible patients will initially receive an induction phase of six 28-day cycles of isatuximab in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd), followed by a maintenance phase with isatuximab and lenalidomide until disease progression, death, unacceptable adverse events, lost to follow up, or consent withdrawal, whichever occurs first. The study will last for approximately 36 months (follow-up period), starting from the date of the first patient in, to the date of the last patient last visit. The primary objective is to assess the effect of induction treatment with isatuximab in combination with VCd on the renal function of newly diagnosed patients with multiple myeloma and severe renal impairment (RI). The secondary objectives are to evaluate the effect of isatuximab in combination with VCd, followed by lenalidomide maintenance on: Overall response rate, Progression-Free Survival, Time to Response, Duration of Response, Overall Survival, Minimal Residual Disease negativity rate, Safety
Cryoglobulinaemia is defined as the presence of immunoglobulins in the serum, which reversibly precipitate and form a gel when the temperature drops below 37°C and redissolve upon re-warming. Classification includes three subgroups based on Immunoglobulin (Ig) composition. Type I cryoglobulinaemia consists of only one isotype or subclass of immunoglobulin. Types II and III are classified as mixed cryoglobulinaemia (MC) because they include both IgG and IgM components. Overall, cryoglobulinaemia is considered a rare disease (<5/10,000 in the general European and North American population), although prevalence is likely to be higher in some areas such as the Mediterranean Basin. MC vasculitis is a multi-organic disease involving kidneys, joints, skin, and peripheral nerves. In type I cryoglobulinaemic vasculitis, searching for an underlying plasma-cell neoplasms is mandatory. Cryoglobulinaemia composed of IgG is more often found in multiple myeloma or monoclonal gammapathy of unknown significance. The course of MC vasculitis varies widely, and the prognosis is influenced by both MC-induced damage to vital organs and co-morbidities associated with underlying diseases. Type I cryoglobulinaemic vasculitis is a plasma cell associated disorder at the crossroad between autoimmunity and plasma-cell neoplasm. Treatment should be modulated according to the underlying associated disease and the severity of internal organ involvement. The overall 10-year survival after a diagnosis of cryoglobulinaemic syndrome ranges from 50% to 90% in case of renal involvement. The main therapeutic goal must be the cure of the underlying haematological disease (overwhelmingly plasma-cell neoplasms). The most common neoplasias are multiple myeloma (predominantly associated with type I cryoglobulinaemia and hyper-viscosity) in more than 50% of cases. Treating the underlying monoclonal disorder has been associated with improvement/stabilization of cryoglobulinaemic symptoms in most patients with type I cryoglobulinemia, although negativation of serum cryoglobulins was achieved in only half the patients. Alkylating agents and bortezomib are the main therapeutic options, but are associated with side effects including neuropathy. Patients presenting with symptomatic hyperviscosity require urgent therapeutic intervention using plasma exchange or plasmapheresis to remove cryoglobulins from the circulation. There is no standard of care or international guidelines for treatment of type 1 cryoglobulinemia. Isatuximab is an anti-CD38 monoclonal antibody that has been effective to treat relapsed or refractory multiple myeloma. Autoreactive plasma cells represent a key player in autoimmune disorders and particularly in type I cryoglobulinemia. Type I cryoglobulinemia is a model of plasma cell associated disorder at the crossroad between autoimmunity and plasma-cell neoplasm. However, rituximab fails to target this population and is poorly effective in this condition. Thus, there is an unmeet need for plasma cell targeted therapy in type I cryoglobulinemia. Clonal plasma cells in type I cryoglobulinemia do express surface CD38, providing a rationale for the use of isatuximab in cryoglobulinemia. Although the biology of the clonal plasma cell in type I cryoglobulinemia is distinct from that of Amyloid light-chain (AL) amyloidosis, they are models of hematological diseases associated with monoclonal Ig and whose tumor mass is low. In AL amyloidosis anti-CD38 targeted therapy was highly efficient as monotherapy in treatment naïve patients and relapsers. Thus, Isatuximab represents a highly promising therapy in type I cryoglobulinemia that could be use as monotherapy. This study is a Phase 2 pilot prospective study of 21 patients with type I cryoglobulinemia treated by Isatuximab. Isatuximab will be given intravenously at 10 mg/kg at day 0, week (W)1, W2, W3, and W4 then every 2 weeks for a total of 12 infusions.