Rituximab + HDMP Debulking Before Venetoclax for Chronic B-Cell Leukemia
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial aims to determine if a combination of rituximab (an antibody therapy) and high-dose methylprednisolone (a corticosteroid) can safely prepare the body for venetoclax treatment in individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The goal is to reduce cancer cell numbers before starting venetoclax, helping to prevent tumor lysis syndrome (TLS), a serious side effect where cancer cells break down too quickly. Participants will be divided into two groups based on their TLS risk: those at high risk will receive the combination treatment first, while those at low risk will start directly with venetoclax. The trial seeks individuals with CLL or SLL who have undergone previous treatment and experience symptoms like swollen lymph nodes or a rapid increase in white blood cells. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications like moderate or strong CYP3A inhibitors or inducers within 7 days before starting venetoclax, and you should avoid grapefruit, Seville oranges, and star fruit within 3 days before starting venetoclax.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that the combination of high-dose methylprednisolone (HDMP) and rituximab is generally well tolerated by patients. One study found this combination promising and well tolerated for treating certain blood cancers.
For venetoclax, studies have demonstrated its effectiveness for chronic lymphocytic leukemia (CLL), though it can cause serious side effects. Many patients experienced very low white blood cell counts, known as neutropenia. Careful monitoring and proper treatment can manage this side effect.
All these drugs have FDA approval for treating CLL, indicating a known safety record when used alone or in some combinations. However, the specific combination and dosing in this trial are experimental, so safety requires close monitoring. Consulting a healthcare professional is essential to understand the potential risks and benefits.12345Why are researchers excited about this trial's treatments?
Researchers are excited about this combination treatment for chronic B-cell leukemia because it introduces a strategic approach by using rituximab and high-dose methylprednisolone (HDMP) for debulking before starting venetoclax. This differs from standard treatments like chemotherapy and single-agent rituximab, as it aims to reduce the tumor burden more effectively before venetoclax targets and kills the remaining cancer cells. Venetoclax specifically inhibits BCL-2, a protein that helps cancer cells survive, offering a targeted mechanism of action that could enhance treatment effectiveness. This approach could potentially lead to faster and more comprehensive responses compared to traditional treatments.
What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?
Research has shown that using rituximab and high-dose methylprednisolone (HDMP) together can effectively reduce cancer cells in people with chronic lymphocytic leukemia (CLL). This combination shrinks tumors without harming the bone marrow. In this trial, participants will receive HDMP and rituximab for debulking before starting venetoclax. Venetoclax alone is known to be very effective against CLL by targeting and killing cancer cells, leading to high remission rates, where disease symptoms disappear. Combining these treatments aims to lower the risk of tumor lysis syndrome (TLS), a serious condition from the rapid breakdown of cancer cells, while effectively managing leukemia. Overall, evidence suggests these treatments work well in reducing cancer and managing related risks.12346
Who Is on the Research Team?
Choi Michael, MD
Principal Investigator
University of California, San Diego
Are You a Good Fit for This Trial?
Adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have had at least one prior treatment but not venetoclax in the last 6 months, can join. They must be generally healthy, understand the study, and agree to use contraception. Excluded are those with severe allergies to monoclonal antibodies, recent heart attacks, uncontrolled infections or other cancers that could interfere.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Debulking Treatment
Patients receive HDMP + Rituximab for 1 cycle to reduce tumor burden before starting venetoclax
Venetoclax Ramp-up
Patients begin venetoclax dose ramp-up after achieving low tumor burden, with a schedule according to venetoclax package insert
Venetoclax Maintenance
Patients continue Venetoclax 400 mg (or highest tolerated dose) for up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- High-Dose Methylprednisolone
- Rituximab
- Venetoclax
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of California, San Diego
Lead Sponsor