CLL (Chronic Lymphocytic Leukemia)

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. ...

This study is a prospective, multicenter, open-label, single-arm phase II clinical trial evaluating the efficacy and safety of an MRD-guided, time-limited therapy with zanubrutinib combined with sonrotoclax in previously untreated high-risk CLL/SLL patients.

The evidence base in support of fixed-duration, first-line approaches in medically fit patients with CLL is clearly strengthening, whether through combining targeted agents with immunochemotherapy or through chemotherapy-free combinations. The long-term PB MRD response rates with the investagators fixed-duration (15-month) immunochemotherapy approach remain the best to date, even compared to the new targeted agent combinations of ibrutinib-venetoclax or obinutuzumab-venetoclax. The investigators' phase 2 ICLL07 trial in previously untreated fit CLL patients with a fixed-duration immunochemotherapy approach (with 4 cycles of FC-obinutuzumab and chemosparing strategy) carries a low risk for short and long term toxicities which still exist, including cardiac toxicities probably related to BTK inhibitors, moreover, two patients experienced treatment related myelodysplastic syndrome or acute myeloid leukemia beyond the end of treatment. Follow-up at 5,5 years from treatment start showed a persistent PB MRD benefit beyond end of treatment, high survival rates, and low long term toxicity with no difference in the durability of MRD response between the mutated and unmutated IGHV patients. The investigators aim to explore the safety and efficacy of a fixed duration strategy combining a new BTK inhibitor with a favorable safety profile and a limited number of ICT courses. The main goals and concerns are: i) to ensure deep response and long lasting MRD ii) to reduce the duration of BTKi exposure and the risk of clonal evolution with the appearance of deleterious mutations iii) to limit the risk of hematopoietic secondary cancers (MDS/AML) by excluding patients in whom clonal hematopoiesis of undetermined potential (CHIP) is detected before inclusion and decreasing the number of courses of chemotherapy to 3 cycles. Moreover, patients with TP53 abnormalities will be excluded with a lower cut off (1% versus 10% in the previous studies) iv) to limit the risk of BTKi toxicity by using a non-covalent BTKi

This is a Phase 3, randomized, open-label, multicenter study comparing rocbrutinib (LP-168) versus pirtobrutinib in adult participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received a covalent Bruton's tyrosine kinase inhibitor (cBTKi). Approximately 306 participants will be randomized 1:1 to receive rocbrutinib 200 mg orally once daily or pirtobrutinib 200 mg orally once daily, administered continuously in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. Randomization will be stratified by presence of del(17p)/TP53 mutation (yes/no), reason for discontinuation of prior cBTKi therapy (toxicity vs disease progression), prior exposure to a BCL2 inhibitor (yes/no), and region (United States/China/rest of world). The primary endpoint is progression-free survival (PFS) assessed by an independent review committee (IRC) using iwCLL 2018 criteria for CLL and Lugano 2014 criteria for SLL. Key secondary objectives include overall survival, overall response rate, time-to-event outcomes, and safety/tolerability; exploratory objectives include health-related quality of life and biomarker assessments.

The goal of this clinical trial is to investigate whether a short-term (4-week) whole-food, plant-based (WFPB) diet has an effect on metabolism, immune function, and disease activity in early-stage chronic lymphocytic leukemia (CLL). The main questions the study aims to answer are: * Does a WFPB diet influence disease progression? * How do CLL cells and other immune cell types respond to a WFPB diet in terms of metabolism and signaling? Researchers will examine whether a WFPB diet can affect absolute lymphocyte counts in participants' blood and what metabolic or functional changes occur within the CLL cells. Participants will: * Switch to a WFPB diet for 4 weeks following an introductory session with a certified dietary instructor. * Visit the clinic before starting the diet and again after 14 and 28 days for blood draws and to provide stool samples. * Keep a diary of all foods and drinks consumed during the week prior to and throughout the study period.

The purpose of this clinical trial is to compare drug combinations to learn which drugs work best to prevent graft-versus-host-disease (GVHD) in people who have received a stem cell transplant. The source of stem cells is from someone who is not related and has a different blood cell type than the study participant. The researchers will compare the new drug combination to a standard drug combination. They will also learn about the safety of each drug combination. Participants will: * Receive the standard or new drug combination after transplant * Visit the doctor's office for check-ups and tests after transplant that are routine for most transplant patients * Take surveys about physical and emotional well-being * Give blood and stool samples.

The goal of this clinical trial is to determine the safety and feasibility of allogeneic transplantation with bone marrow from a deceased donor in patients with acute and chronic leukemias, myelodysplastic syndrome, and certain lymphomas. Patients will either receive myeloablative conditioning or reduced intensity conditioning regimen prior to the transplant. Patients will be followed for 56 days for safety endpoints and remain in follow-up for one year.

This is a clinical study aiming to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ZE50-0134 in relapsed and refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, and select low-grad lymphomas.

A Phase Ib Study of the Selective PKC-β Inhibitor MS-553 in Patients with Refractory or Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma