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

Overseen By Julie Vo

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Diego

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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 the combination of Rituximab and Venetoclax safe for treating chronic lymphocytic leukemia?

The combination of Rituximab and Venetoclax has been shown to have a manageable safety profile in clinical trials for chronic lymphocytic leukemia, with the addition of Rituximab being well tolerated in patients who initially progressed on Venetoclax alone. ^{1 2 3 4 5}

How is the drug combination of Rituximab, HDMP, and Venetoclax unique for treating chronic B-cell leukemia?

This treatment is unique because it combines Rituximab and Venetoclax, which have shown synergistic effects in prolonging progression-free survival, with High-Dose Methylprednisolone (HDMP) for debulking (reducing tumor size) before starting Venetoclax. This approach may enhance the effectiveness of Venetoclax, especially in patients who have relapsed or have refractory chronic lymphocytic leukemia. ^{1 3 4 5 6}

What data supports the effectiveness of the drug combination of rituximab and venetoclax for chronic B-cell leukemia?

Research shows that combining rituximab with venetoclax can be effective for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). In studies, this combination provided longer progression-free survival (the time during which the disease does not get worse) compared to venetoclax alone, and many patients experienced significant and lasting responses. ^{1 3 4 5 7}

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

I have recovered from side effects of my previous treatments.

I agree not to become pregnant during the study.

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

Exclusion Criteria

History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

I have not taken certain medications recently.

I currently have an active infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Debulking Treatment

Patients receive HDMP + Rituximab for 1 cycle to reduce tumor burden before starting venetoclax

4 weeks

Venetoclax Ramp-up

Patients begin venetoclax dose ramp-up after achieving low tumor burden, with a schedule according to venetoclax package insert

4-6 weeks

Venetoclax Maintenance

Patients continue Venetoclax 400 mg (or highest tolerated dose) for up to 2 years

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

What Are the Treatments Tested in This Trial?

Interventions

• High-Dose Methylprednisolone
• Rituximab
• Venetoclax

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

In a study involving 10 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), the addition of rituximab to venetoclax therapy resulted in a 50% response rate, with three patients achieving complete responses and two achieving partial responses.

The combination treatment was well tolerated, suggesting that adding rituximab after progression on venetoclax may provide a beneficial option for some patients with R/R CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy. Handunnetti, S., Anderson, MA., Roberts, AW., et al.[2022]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

In a study of 323 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), a daily dose of 400 mg of venetoclax resulted in a median progression-free survival (PFS) of 1.8 years.

The addition of 6 cycles of rituximab to venetoclax treatment significantly increased the median PFS to 3.9 years, demonstrating a synergistic effect that enhances treatment efficacy beyond increasing the venetoclax dose alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. Freise, KJ., Jones, AK., Menon, RM., et al.[2018]

The combination of venetoclax with rituximab showed remarkable efficacy and a manageable safety profile in treating chronic lymphocytic leukemia (CLL), both in relapsed/refractory cases and as a first-line therapy for high-risk patients.

Similarly, the combination of ibrutinib with venetoclax also demonstrated striking efficacy, suggesting that these combinations could become new standard treatment options for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. Wanner, D., Steurer, M.[2020]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Addition of rituximab in relapsed/refractory chronic lymphocytic leukemia after progression on venetoclax monotherapy. [2022]

2. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Relationship between venetoclax exposure, rituximab coadministration, and progression-free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of venetoclax plus rituximab for relapsed CLL: 5-year follow-up of continuous or limited- duration therapy. [2023]

5. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. [2022]