Ongoing Clinical Trials for Lymphocytic Lymphoma

This article provides detailed information about 4 ongoing clinical trials for lymphocytic lymphoma, focusing on treatment options for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). These trials are testing various combinations of medications including ibrutinib, venetoclax, obinutuzumab, and rituximab for both newly diagnosed and relapsed/refractory disease. All trials are currently being conducted in Italy.

Clinical trial locations

• Italy
  • Study of Ibrutinib and Obinutuzumab for Patients with Chronic Lymphocytic Leukemia Who Have Not Received Treatment Before
  • Study of Ibrutinib for Patients with Chronic Lymphocytic Leukemia and TP53 Mutations
  • Study of Venetoclax, Ibrutinib, and Rituximab for Patients with Untreated Chronic Lymphocytic Leukemia
  • Study on Ibrutinib and Venetoclax for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia

Study of Ibrutinib and Obinutuzumab for Patients with Chronic Lymphocytic Leukemia Who Have Not Received Treatment Before

This trial is designed for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who have never received treatment before. The study evaluates the combination of two medications: ibrutinib, which is taken as a pill, and obinutuzumab, which is given through a vein.

Main inclusion criteria: Participants must be 18 years or older with a confirmed diagnosis of active and untreated CLL or SLL that requires treatment. They need to have measurable lymph node disease larger than 1.5 cm and an ECOG performance status of 0 or 1, meaning they can be fully active or have some symptoms but can still do light work. Adequate blood counts are required, including an absolute neutrophil count greater than 750 cells per microliter, a platelet count greater than 30,000 per microliter, and hemoglobin greater than 8.0 grams per deciliter. Liver and kidney function must also be adequate.

Main exclusion criteria: Patients with a different type of cancer than CLL or SLL cannot participate. Those unable to follow study procedures, pregnant or breastfeeding women, patients participating in other trials, those recovering from major surgery, patients with allergic reactions to the study medications, those with substance abuse history, or those with active infections requiring treatment are excluded.

Treatment focus: The study aims to assess how effectively this combination reduces cancer cells in the bone marrow. Patients will receive ibrutinib continuously over 24 cycles, while obinutuzumab is administered during specific cycles. The treatment focuses on achieving minimal residual disease, which means reducing cancer cells to very low, almost undetectable levels. Evaluation occurs 30 days after treatment completion.

Investigational drugs: Ibrutinib works by blocking a specific protein that helps cancer cells grow, potentially slowing down or stopping disease progression. Obinutuzumab is an antibody therapy that targets cancer cells, helping the immune system destroy them more effectively.

Study of Venetoclax, Ibrutinib, and Rituximab for Patients with Untreated Chronic Lymphocytic Leukemia

This trial tests a three-medication combination for patients with CLL who have not received any previous treatment. The study uses venetoclax, rituximab, and ibrutinib in a specific sequence to achieve the best possible response.

Main inclusion criteria: Participants must be between 18 and 64 years old with CLL or SLL requiring treatment. They must not have received any prior treatment for their condition. Adequate bone marrow function is essential, including an absolute neutrophil count of at least 1.0 x 109/L, a platelet count of at least 25 x 109/L, and hemoglobin level of at least 8.0 g/dl. Both men and women can participate, and they must not be part of a vulnerable population.

Main exclusion criteria: Patients who have already received treatment for CLL, those not within the specified age range, and individuals belonging to vulnerable populations cannot participate.

Treatment focus: The trial aims to determine how effectively this three-drug combination reduces cancer cells to minimal residual disease levels. Treatment begins with venetoclax, followed by the addition of rituximab in a delayed manner, and then ibrutinib for consolidation. The goal is to achieve undetectable levels of disease, which will be assessed up to three months after completing the combined therapy using specialized testing methods. The treatment can last up to 24 months with regular monitoring throughout.

Investigational drugs: Venetoclax helps kill cancer cells by inhibiting a survival protein called BCL-2. Rituximab targets specific proteins on cancer cell surfaces, leading to their destruction. Ibrutinib stops cancer cell growth and spread by blocking Bruton’s tyrosine kinase, a protein involved in cancer cell survival.

Study of Ibrutinib for Patients with Chronic Lymphocytic Leukemia and TP53 Mutations

This study focuses specifically on CLL patients with TP53 aberrations, which are genetic changes that can affect how the disease progresses. The trial examines how the genetic makeup of cancer cells changes over time when treated with ibrutinib.

Main inclusion criteria: Participants must be 18 years or older with documented CLL diagnosis. They must not have received previous treatment for CLL, except for steroid treatment used to manage autoimmune issues. Patients must have progressive disease requiring treatment and test negative for certain hepatitis viruses, including HBsAg and either HBcAb or HBV DNA, as well as HCV antibody or HCV RNA. For a specific study group, there must be evidence of a small group of cells with TP53 deletion detected by specialized testing.

Main exclusion criteria: Patients without CLL, those without TP53 mutations, individuals not in the specified age range, patients not experiencing disease progression, and those in vulnerable populations are excluded.

Treatment focus: The study monitors how the size of TP53 mutated subclones changes in response to ibrutinib treatment. Participants receive ibrutinib as their first treatment, with monitoring at multiple time points: weeks 2, 4, 12, 24, 48, 72, and 96, and then annually until the study ends or disease progression occurs. This helps researchers understand ibrutinib’s effectiveness in managing CLL with these specific genetic changes.

Investigational drug: Ibrutinib blocks a protein called Bruton’s tyrosine kinase that helps cancer cells grow and survive, potentially slowing or stopping disease progression in patients with TP53 mutations.

Study on Ibrutinib and Venetoclax for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia

This trial is designed for patients whose CLL has returned after treatment or has not responded to previous therapies. It tests the combination of ibrutinib and venetoclax to determine if this approach can reduce cancer cells to minimal levels.

Main inclusion criteria: Patients must have confirmed CLL requiring treatment, with relapsed or refractory disease after at least one prior therapy. They must be between 18 and 65 years old with adequate bone marrow function, including an absolute neutrophil count of at least 1.0 x 109/L, a platelet count of at least 30 x 109/L (or 20 x 109/L if low count is due to bone marrow involvement), and hemoglobin level of at least 8.0 g/dl. Both male and female patients can participate, and they should not belong to a vulnerable population.

Main exclusion criteria: The trial excludes patients without documented relapsed or refractory CLL, those outside the specified age range, and individuals unable to provide informed consent.

Treatment focus: The study evaluates how effectively adding ibrutinib to venetoclax achieves minimal residual disease negativity, meaning cancer cells are reduced to almost undetectable levels. Treatment begins with venetoclax administered orally, followed by the addition of ibrutinib. Response is regularly monitored using specialized multi-color flow cytometry analysis. The treatment strategy is guided by the level of remaining cancer cells in the body, with adjustments made based on patient response and tolerance.

Investigational drugs: Ibrutinib blocks Bruton’s tyrosine kinase, a protein involved in cancer cell growth and survival. Venetoclax targets and blocks BCL-2, a protein that prevents cancer cells from dying, helping eliminate these cells from the body. The trial assesses how well this combination works using a strategy guided by minimal residual disease monitoring.

Summary

All four clinical trials for lymphocytic lymphoma are currently being conducted in Italy, indicating a concentration of research activity in this region. Three of the four trials focus on previously untreated patients, offering insights into first-line treatment strategies, while one trial specifically addresses relapsed or refractory disease. A notable observation is the prominent role of ibrutinib, which appears in all four trials, either as monotherapy or in combination with other medications. Venetoclax features in two trials, both exploring its use in combination therapy. The studies employ various approaches, including two-drug combinations and triple-therapy regimens, reflecting the ongoing search for optimal treatment strategies. One trial specifically targets patients with TP53 mutations, a genetic change associated with more challenging disease. All trials share a common goal of achieving minimal residual disease, which represents a very low level of remaining cancer cells and is considered an important treatment outcome. The age ranges vary across trials, with some accepting patients up to age 64 or 65, while others have no upper age limit beyond 18 years.