Venetoclax + Rituximab for Chronic Lymphocytic Leukemia

Recruiting at 1 trial location

Overseen By Jenny Crawford, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Recent transplant, Uncontrolled infections, Liver disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multicenter, Phase II study to investigate the efficacy and safety of venetoclax in combination with Rituximab/hyaluronidase human in participants with relapsed or refractory chronic lymphocytic leukemia (CLL).

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that certain medications, like strong CYP3A inhibitors and inducers, should not be taken within 7 days before starting the trial. If you're on warfarin, you may be encouraged to switch to another anticoagulant.

What data supports the effectiveness of the drug combination Venetoclax and Rituximab for treating Chronic Lymphocytic Leukemia?

Research shows that the combination of Venetoclax and Rituximab is effective in treating relapsed or refractory chronic lymphocytic leukemia (CLL). This combination has been shown to prolong the time patients live without the disease getting worse and can lead to deep responses, meaning the cancer is less detectable in the body. The combination is more effective than some other treatments and has a manageable safety profile. ^{1 2 3 4 5}

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

The combination of Venetoclax and Rituximab has been shown to have a manageable safety profile in clinical trials for relapsed or refractory chronic lymphocytic leukemia. Studies indicate that this treatment is generally well-tolerated, with no significant safety concerns related to severe infections or neutropenia (low white blood cell count). ^{1 2 5 6 7}

How is the drug combination of Venetoclax and Rituximab unique for treating chronic lymphocytic leukemia?

The combination of Venetoclax and Rituximab is unique because Venetoclax is a first-in-class oral drug that selectively inhibits BCL-2, a protein that helps cancer cells survive, and when combined with Rituximab, it has shown to be more effective than some traditional treatments in prolonging progression-free survival and achieving undetectable levels of cancer cells in the blood and bone marrow. ^{1 2 5 8 9}

Research Team

Kieron Dunleavy, MD

Principal Investigator

Georgetown University

Eligibility Criteria

This trial is for adults with relapsed or refractory chronic lymphocytic leukemia (CLL). Participants must have adequate organ function, an ECOG score ≤ 2 indicating they can perform daily activities with some limitations, and agree to contraception if applicable. Exclusions include other active cancers, significant uncontrolled diseases, certain infections like hepatitis B/C or HIV not under control, recent major surgery, pregnancy, and known allergies to study drugs.

Inclusion Criteria

My condition has worsened or not improved after treatment.

I have HIV but it's under control with my current treatment.

I am taking warfarin but am open to switching to another blood thinner if needed.

Exclusion Criteria

Known infection with human T-cell leukemia virus 1 (HTLV-1)

You have a known allergy or sensitivity to any of the study medications.

I had skin cancer or early-stage melanoma or cervical cancer treated to cure, or any cancer treated with surgery only, and have been in remission for 2+ years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ramp-up Treatment

Participants undergo a 5-week ramp-up period with venetoclax, starting at 20 mg and increasing to 400 mg

5 weeks

Weekly visits for dose escalation

Combination Treatment

Participants receive venetoclax 400 mg daily and rituximab/hyaluronidase human as per protocol

6 cycles (28 days each)

Cycle 1: 1 visit (IV), Cycles 2-6: 1 visit (SC) each

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

End of treatment visit

Long-term Follow-up

Participants are monitored for disease progression or death

Up to 5 years

Treatment Details

Interventions

• Rituximab
• Rituximab/Hyaluronidase Human
• Venetoclax

Trial Overview The trial tests the effectiveness and safety of combining venetoclax with Rituximab/hyaluronidase human in treating CLL that has returned after treatment or did not respond to previous treatments. It's a Phase II study where all participants receive the same combination therapy without being compared to another group.

Participant Groups

Group I: Venetoclax + Rituximab Experimental Treatment 3 Interventions

Participants will be initially placed in a venetoclax 5 weeks ramp-up period, and will be administered an initial 20 mg oral tablet dose once daily (QD), incrementing weekly up to a maximum dose of 400 mg. Participants will then continue taking venetoclax 400 mg QD from Week 5 onwards, as directed by the investigator in combination with rituximab 375 mg/m\^2 IV on Day 1 of Cycle 1 followed by 13.4 mL of rituximab SC 1,600 mg/26,800 Units vial (1,600 mg rituximab and 26,800 Units hyaluronidase human) on Day 1 of Cycle 2-6.

Rituximab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Hackensack Meridian Health

Collaborator

Trials

141

Recruited

42,900+

Findings from Research

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]

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]

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]

Ibrutinib has shown durable efficacy in treating relapsed/refractory chronic lymphocytic leukemia (CLL) over a 7-year follow-up, but patients with certain health conditions like cardiac disease or those on anticoagulants may not be suitable for this continuous therapy.

Venetoclax combined with rituximab offers an effective, chemo-free treatment option for R/R CLL with a fixed duration of up to 24 months, achieving deep responses in most patients and demonstrating a reassuring safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapsed/Refractory Chronic Lymphocytic Leukemia: Chemoimmunotherapy, Treatment until Progression with Mechanism-Driven Agents or Finite-Duration Therapy? Cuneo, A., Foà, R.[2020]

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]

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]

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [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. Italy pubmed.ncbi.nlm.nih.gov

Relapsed/Refractory Chronic Lymphocytic Leukemia: Chemoimmunotherapy, Treatment until Progression with Mechanism-Driven Agents or Finite-Duration Therapy? [2020]

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

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

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

Exposure-response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: pooled results from a phase 1b study and the phase 3 MURANO study. [2022]

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

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

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

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]