What side effects are associated with this type of intervention?

Common treatments for Lymphocytic Leukemia/Lymphoma, such as Rituximab and High Dose Methylprednisolone (HDMP), have several known side effects. Rituximab can cause infusion reactions, prolonged neutropenia, hypogammaglobulinemia, and increased risk of infections. High Dose Methylprednisolone can lead to hyperglycemia, hypertension, increased risk of infections, osteoporosis, and gastrointestinal issues. Combining these treatments may increase the risk of infections and other immune-related side effects.

What prior FDA approvals exist?

Rituximab, a monoclonal antibody targeting CD20 on B-cells, has been FDA-approved for the treatment of various types of lymphocytic leukemia and lymphoma, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). It is often used in combination with chemotherapy agents such as fludarabine, cyclophosphamide, and bendamustine. High Dose Methylprednisolone (HDMP), a corticosteroid, is used to reduce inflammation and modulate the immune response, and while not specifically approved as a standalone treatment for lymphocytic leukemia/lymphoma, it is commonly used in combination with other therapies to enhance their efficacy. Other related FDA-approved drugs include ibrutinib and venetoclax, which are used in combination with rituximab for CLL treatment.

What other types of research exist?

Promising novel alternatives to Rituximab and HDMP for Lymphocytic Leukemia/Lymphoma patients include: 1) Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, which has shown efficacy in CLL/SLL. 2) Venetoclax, a BCL-2 inhibitor, which is effective in inducing apoptosis in cancer cells. 3) CAR T-cell therapies, such as KTE-X19, which have shown significant activity in relapsed or refractory cases. 4) Obinutuzumab, a glycoengineered anti-CD20 monoclonal antibody, which may offer enhanced efficacy over Rituximab.

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Corticosteroid

Rituximab + HDMP Debulking Before Venetoclax for Chronic B-Cell Leukemia

Phase 1

Waitlist Available

Led By Choi Michael, MD

Research Sponsored by University of California, San Diego

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Women of child-bearing potential must agree to not become pregnant for the duration of the study

Patients must be age 18 or older

Must not have

Known active bacterial, viral, fungal, mycobacterial, or other infection

Women who are pregnant or lactating

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if using rituximab and high dose methylprednisolone together can reduce cancer cells in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. The goal is to make venetoclax safer by lowering the risk of a serious side effect. Patients will be divided into groups based on their risk and treated accordingly. Rituximab is effective in treating various lymphomas and leukemias.

Who is the study for?

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.

What is being tested?

The trial tests if rituximab combined with high-dose methylprednisolone (HDMP) can reduce cancer cells before starting venetoclax for CLL/SLL patients. Depending on their risk of tumor lysis syndrome (TLS), participants will either receive HDMP/rituximab first or start directly on venetoclax. The goal is to see if this reduces TLS risk when beginning venetoclax therapy.

What are the potential side effects?

Possible side effects include kidney problems or abnormal heart rhythms due to rapid cancer cell breakdown (TLS). Other risks may involve reactions related to infusion treatments and the individual drugs' typical side effects like immune system impacts and organ inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I agree not to become pregnant during the study.

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I am 18 years old or older.

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My cancer is classified as medium or high in terms of how much it has spread.

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I have been diagnosed with CLL or SLL.

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I agree to use barrier methods for birth control.

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I can take care of myself and perform daily activities.

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My condition requires treatment for CLL or SLL as per international guidelines.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I currently have an active infection.

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I am not pregnant or breastfeeding.

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I am HIV positive.

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My diabetes is not well-controlled.

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I haven't had a heart attack or significant heart disease in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of patients that have a decrease in tumor burden from levels of disease that meet "Medium/High-tumor burden" criteria to meet "Low tumor burden" criteria for disease burden following 1 or 2 cycles of HDMP + Rituximab.

Secondary study objectives

Adverse events by CTCAE4 definitions

Overall Response rate, Partial Response rate, and Complete response rate per iwCLL criteria after 9 months of venetoclax and at completion of treatment

Percentage of patients that have a decrease in tumor burden from levels of disease that meet "Medium/High-tumor burden" c criteria to meet "Low tumor burden" criteria for disease burden following 1 cycle of HDMP + Rituximab.

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Arm AExperimental Treatment1 Intervention

HDMP + rituximab as a means of debulking prior to initiating venetoclax.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Rituximab, a monoclonal antibody, targets the CD20 antigen on B-cells, leading to their destruction through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). High Dose Methylprednisolone (HDMP) is a corticosteroid that reduces inflammation and modulates the immune response, helping to decrease tumor burden and alleviate symptoms. These mechanisms are vital for Lymphocytic Leukemia/Lymphoma patients as they directly target malignant B-cells and manage disease symptoms, improving overall outcomes and quality of life.

Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia.Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis.