Clinical Research Directory

Study to Assess Change in Disease Activity of Oral Venetoclax in Adult Participants With Recurring Relapsed or Refractory (R/R) Waldenström Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)

Lymphoplasmacytic Lymphoma (LPL) is a rare type of low-grade B-cell lymphoma. The purpose of this study is to assess the change in disease activity of adult participants with relapsed or refractory Waldenström macroglobulinemia(WM)/LPL receiving venetoclax. Venetoclax is being investigated in the treatment of WM/LPL. Participants will receive oral venetoclax at doses ramping up to the target dose, as part of treatment. Approximately 14 adult participants with WM/LPL will be enrolled in the study at approximately 20 sites in Japan. Participants will receive oral venetoclax at doses ramping up to the target dose. The total study duration is approximately 28 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, and checking for side effects.

Pirtobrutinib and Venetoclax in Waldenström Macroglobulinemia

This study is being done to examine the safety and effectiveness of pirtobrutinib combined with venetoclax as a possible treatment for participants with Waldenström Macroglobulinemia (WM). The names of the study drugs involved in this study are: * Pirtobrutinib (a Noncovalent Bruton Tyrosine Kinase (BTK) inhibitor) * Venetoclax (a BCL2 inhibitor)

Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma

This phase II trial studies the effects of venetoclax and rituximab in comparison to ibrutinib and rituximab or zanubrutinib in treating patients with previously untreated Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called BTK, which may help keep cancer cells from growing. Giving venetoclax and rituximab may work better in treating patients with previously untreated Waldenstrom's macroglobulinemia than ibrutinib with rituximab or zanubrutinib alone.

Rifaximin in Patients With Monoclonal Gammopathy

This trial studies how well rifaximin works in treating patients with monoclonal gammopathy. Antibiotics, such as rifaximin, may help to kill bacteria in the intestines and reduce the abnormal protein or cells in patients with monoclonal gammopathy.

Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

Background The development of new technologies now allow scientists to investigate the molecular basis and clinical manifestations of monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL). Applying these methods in a natural history study can help identify processes involved in disease progression, and possibly lead to the discovery or validation of treatment targets. Objectives Study the history of MBL/CLL/SLL/LPL/WM/SMZL in patients prior to and after treatment. Characterize clinical, biologic and molecular events of disease stability and progression of patients enrolled on this protocol. Eligibility: * Diagnosis of CLL/SLL and on treatment/previously treated/nearing treatment * Diagnosis of LPL/WM * As of February 5, 2025, patients with MBL and SMZL will no longer be enrolled. * Age greater than or equal to 18 years. * ECOG performance status of 0-2. Design Patients are typically followed every 6 to 24 months in the clinic and have blood drawn. Patients may be asked to undergo additional testing, including bone marrow biopsy and aspiration, lymph node biopsy, positron emission tomography, and CT and MRI scans. Some of these tests (e.g., blood draw) may be required to monitor CLL/SLL and LPL/WM. Other tests (e.g., lymph node biopsy) may not be clinically indicated, but patients may be asked to undergo these procedures for research purposes. No treatment will be administered on this study. If a patients requires treatment for their cancer, available NIH clinical trials and alternative treatment options will be discussed with the patient.

Loncastuximab Tesirine in WM

This study is being done to examine the safety and effectiveness of loncastuximab tesirine as a possible treatment for participants with Waldenström Macroglobulinemia (WM). The name of the study drug involved in this study is: * Loncastuximab tesirine

A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )

The purpose of this study is to find the best dose of the drug and measure the safety and efficacy of LY4152199 in participants with previously treated B-cell malignancies. Participants will have the option to continue taking LY4152199 until the study ends.

Efficacy and Safety of Carfilzomib in Combination With Ibrutinib vs Ibrutinib in Waldenström's Macroglobulinemia

In Waldenström macroglobulinemia (WM) chemotherapy induces only low CR/VGPR (Complete Remission/ Very Good Partial Response) rates and responses of short duration compared to other indolent lymphomas. Thus, innovative approaches are needed which combine excellent activity and tolerability in WM. Chemotherapy-free approaches are highly attractive for this patient group. Based on its high activity in WM and its low toxicity, Ibrutinib was approved for the treatment of WM by the European Medicines Agency (EMA). However, also Ibrutinib fails to induce CRs and the VGPR rate is 16% in relapsed patients. In addition, activity of Ibrutinib depends on the genotype: compared to MYD88mut/CXCR4WT patients Ibrutinib single agent therapy induces substantially lower response rates in patients with the MYD88mut/CXCR4mut or the MYD88WT/CXCR4WT genotype (major response (at least PR) in 91.7 % compared to 61.9 and 0 %, respectively). Phase II data have indicated that the proteasome inhibitor Carfilzomib is able to overcome the inferior prognosis of Ibrutinib in MYD88mut/CXCR4mut and MYD88WT/CXCR4WT patients, as response rates were high for all genotypes in a phase II study combining Carfilzomib with Rituximab and Dexamethasone. Based on this the investigators hypothesize that addition of Carfilzomib to Ibrutinib will increase the VGPR/CR rate compared to Ibrutinib alone in patients with WM, in particular in patients carrying the CXCR4 mutation. In addition, the investigators hypothesize, that the combination Carfilzomib and Ibrutinib will be also highly active in MYD88 wildtype patients and that this combination will be at least as efficient in treatment naïve patients as in relapsed/refractory patients.

Ibrutinib + Venetoclax in Untreated WM

This study evaluates the safety and efficacy of Ibrutinib combined with Venetoclax (IVEN) in the treatment of adults diagnosed with Waldenstrom's macroglobulinemia (WM) cancer with a specific MYD88 gene mutation. This research study involves an experimental drug combination of targeted therapies. The names of the study drugs involved in this study are: * Venetoclax * ibrutinib

A Long-term Extension Study of PCI-32765 (Ibrutinib)

The purpose of this study is to collect long-term safety and efficacy data for participants treated with ibrutinib and to provide ongoing access to ibrutinib for participants who are currently enrolled in ibrutinib studies that have been completed according to the parent protocol, are actively receiving treatment with ibrutinib, and who continue to benefit from ibrutinib treatment.

Study of MGUS, Smoldering Myeloma, Early MDS and CLL to Assess Molecular Events of Progression and Clinical Outcome

Blood cancers occur when the molecules that control normal cell growth are damaged. Many of these changes can be detected by directly examining parts of the cancer or cells in blood. Several alterations that occur repeatedly in certain types of blood cancers have already been identified, and these discoveries have led to the development of new drugs that target those alterations. More remain to be discovered. Some of these abnormalities include alterations in genes. Genes are the part of cells that contain the instructions which tell the investigators bodies how to grow and work, and determine physical characteristics such as hair and eye color. Genes are composed of DNA letters that spell out these instructions. Studies of the DNA molecules that make up the genes are called "molecular" analyses. Molecular analyses are ways of reading the DNA letters to identify errors in genes that may contribute to an increased risk of cancer or to the behavior of the cancer cells. Some changes in genes occur only in cancer cells. Others occur in the genes that are passed from parent to child. This research study will examine both kinds of genes. The best way to find these genes is to study large numbers of people. The investigators expect that as many 1000 individuals will enroll in this study. This research study is trying to help doctors and scientists understand why cancer occurs and to develop ways to better treat and prevent it. To participate in this study the participant must have cancer now, had it in the past, or are at risk of developing cancer. The participant will not undergo tests or procedures that are not required as part of their routine clinical care. The investigators will ask the participant to provide an additional sample from tissue that is obtained for their clinical care including blood, bone marrow, or tissue sample. The investigators will also ask for a gentle scrape of the inside of their cheek, mouthwash or a skin sample to obtain their germline DNA

Ibrutinib and Ixazomib Citrate in Treating Newly Diagnosed, Relapsed or Refractory Waldenstrom Macroglobulinemia

This phase II trial studies the side effects of ibrutinib citrate when given with ixazomib, and determines how well they work in treating patients with Waldenstrom macroglobulinemia that is newly diagnosed, has come back (recurrent) or does not respond to treatment (refractory). Enzyme inhibitors, such as ibrutinib and ixazomib citrate, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Efficacy of Venetoclax in Combination With Rituximab in Waldenström's Macroglobulinemia

In Waldenström's macroglobulinemia (WM) chemotherapy induces only low CR/VGPR rates and response duration is limited. In addition, WM patients are often elderly, partly not tolerating chemotherapy related toxicities. Thus, innovative approaches are needed which combine excellent activity and tolerability in WM. Chemotherapy-free approaches are highly attractive for this patient group. Based on its high activity and favorable toxicity profile in indolent B-NHL such as CLL, Venetoclax was approved for the treatment of this diseases by the FDA and the European Medicines Agency (EMA). First data in relapsed/refractory WM have documented high activity and low toxicity of Venetoclax also in WM, including patients with prior Ibrutinib treatment or patients carrying CXCR4 mutations. Ibrutinib itself has high activity and a relatively low toxicity profile in WM, but has also major disadvantages: the main disadvantage is the need to apply this drug continuously. Furthermore, Ibrutinib efficacy depends largely on the genotype with a substantial drop in major responses and PFS in the presence of CXCR4 mutations and non-mutated MYD88. In particular the need of continuous treatment for Ibrutinib has prevented that Ibrutinib has become the standard of care outcompeting conventional Rituximab/chemotherapy. This is reflected in current guidelines such as the NCCN and the ESMO guidelines, which still see immunochemotherapy as a backbone of treatment, largely because of the advantage of a timely fixed application. Data in CLL in the relapsed as well as in the first line setting have convincingly shown that in contrast to Ibrutinib Venetoclax is highly efficient also when used in a timely defined application scheme over 12 months in combination with the anti-CD20 antibody Rituximab. Data documented deep responses including molecular responses and a highly significant advantage over immunochemotherapy in large international Phase III trials, changing the standard of care in this disease. Based on this the hypothesis is that timely fixed application of the combination of Venetoclax and Rituximab induces significantly superior treatment outcomes compared to chemotherapy and Rituximab (DRC) in patients with treatment naïve WM, regardless of the genotype. A first indication for this assumption in the proposed trial will allow the performance of confirmatory phase 3 trials that might change the standard of care in WM.

Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Hematologic Cancer

Background: * Individuals may be prone to develop blood or lymph node cancers (leukemia or lymphoma) for a variety of reasons, including genetic predisposition to these cancers, environmental exposures or other medical conditions. * Studies of people and families at high risk of cancer often lead to clues about their cause that may also be important regarding the sporadic occurrence of these cancers in the general population. * Identifying genetic or environmental factors that play a role in the development of these diseases may be important in developing prevention trials, screening programs and treatments. Objectives: * Describe the cancers and other conditions in families with blood or lymph node cancer. * Find and describe genes that may cause blood and lymph node cancer, and understand how they work in families. * Use laboratory methods to try to determine if it is possible to identify who is at highest risk of blood or lymph node cancer. * Test how genes act with other factors to alter the risk of disease, its severity or its manifestations in families. Eligibility: * Individuals of any age with a personal or family history of a blood or lymph node cancer. * Individuals with a personal or family history of medical conditions or environmental exposures that may predispose to blood or lymph node cancer. Design: * Participants complete questionnaires about their personal and family medical history and provide consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with blood or lymph node cancer, tumors, or other related illnesses for whom they are the legally authorized representative. * Participants donate a sample of blood or cheek cells, or a lock of hair for genetic studies. * Patients may also be evaluated at the NIH Clinical Center by one or more of the following specialists: cancer doctor or blood specialist, medical geneticist, research nurses or clinical social worker. They may have blood and urine tests and a cheek swab or mouth wash to collect cheek cells. Some patients may also be asked to have x-rays and routine imaging, such as CT scans or ultrasound tests, cell surface markers, skin biopsy, and, with special consents, bone marrow biopsy, MRI or PET scans, apheresis or fluorescein angiography and photography.

Mosunetuzumab in Combination With Pirtobrutinib in Patients With Relapsed or Refractory Waldenstrom Macroglobulinemia (MPOWER)

The purpose of this clinical trial it to test the safety and tolerability of the study drugs mosunetuzumab in combination with pirtobrutinib in patients with relapsed or refractory Waldenstrom's Macroglobulinemia.

NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers

This is a single arm, open-label, multi-center, Phase 1 study to determine the safety and tolerability of an experimental therapy called NKX019 (allogeneic CAR NK cells targeting CD19) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B cell acute lymphoblastic leukemia (B-ALL)

Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.

SynKIR-310 for Relapsed/Refractory B-NHL

This first-in-human (FIH) trial is designed to assess the safety, feasibility and preliminary efficacy of a single intravenous (IV) dose of SynKIR-310 administered to participants with relapsed/refractory B-NHL.

Zanubrutinib, Bendamustine, Rituximab Prev. Untreated WM

The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM). The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.

Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma

This phase I trial studies the side effects and best dose of BTK inhibitor PCI-32765 when given together with rituximab and bendamustine hydrochloride in treating patients with recurrent non-Hodgkin lymphoma (NHL). BTK inhibitor PCI-32765 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving BTK inhibitor PCI-32765 together with rituximab and bendamustine hydrochloride may kill more cancer cells.

Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom

Part A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy study evaluating IV administration of iopofosine I 131 in patients with WM that have received at least two prior lines of therapy.

Epcoritamab in Previously Treated WM

This study is being done to determine if epcoritamab can be used to treat participants with previously treated Waldenstrom Macroglobulinemia (WM). The names of the study drug involved in this study is: -Epcoritamab (a type of antibody)

Nemtabrutinib, Bortezomib, and Rituximab for WM

This is a phase II (2 parts), open-label, single arm, multicenter study to evaluate the efficacy and safety of nemtabrutinib in combination with bortezomib and rituximab

Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma

This phase II trial studies how well ixazomib citrate and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that grows slowly (indolent). Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving ixazomib citrate together with rituximab may work better in treating indolent B-cell non-Hodgkin lymphoma.