230 Participants Needed

Triple Combo Therapy for Chronic Lymphocytic Leukemia

Recruiting at 9 trial locations
AZ
JD
Cayuga Health Welcomes Dr. Anthony Mato ...
Overseen ByAnthony Mato, MD
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the rate of minimum residual disease (MRD) negative response (i.e. the rate of no evidence of disease) of the study drugs, zanubrutinib, obinutuzumab, and venetoclax, given in combination as a treatment for CLL and/or SLL.

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

The trial protocol does not specify if you must stop all current medications, but certain medications are restricted. You must stop taking strong or moderate inhibitors or inducers of CYP3A, CYP2C8, CYP2C9, and CYP2C19 within 7 days before the trial. You also cannot take warfarin, immunotherapy, hormone therapy (except contraceptives, hormone replacement, or megestrol acetate), or any therapies for lymphoma/leukemia outside of this study. Additionally, avoid grapefruit, Seville oranges, and star fruit within 3 days before the trial.

What data supports the idea that Triple Combo Therapy for Chronic Lymphocytic Leukemia is an effective treatment?

The available research does not provide any data on the effectiveness of Triple Combo Therapy for Chronic Lymphocytic Leukemia. The studies listed focus on other treatments and conditions, such as lupus nephritis, rheumatoid arthritis, and systemic lupus erythematosus, but do not mention the specific combination of drugs used in Triple Combo Therapy for Chronic Lymphocytic Leukemia.12345

What safety data is available for the triple combo therapy for CLL?

The safety data for the combination of venetoclax (Venclexta, Venclyxto) and obinutuzumab (Gazyva) in treating chronic lymphocytic leukemia (CLL) is primarily derived from the CLL14 trial. This trial showed that the combination had an acceptable tolerability profile, with notable adverse events such as grade 3 or 4 neutropenia, which can be managed with supportive therapy and dose modifications. The incidence of grade 3-4 neutropenia was reported to be between 52.8% and 57.7%. Venetoclax has been shown to be effective and safe in both previously untreated and relapsed/refractory CLL, providing durable responses with a manageable safety profile.678910

Is the drug combination of Obinutuzumab, Venetoclax, and Zanubrutinib a promising treatment for Chronic Lymphocytic Leukemia?

Yes, the combination of Obinutuzumab, Venetoclax, and Zanubrutinib is promising for treating Chronic Lymphocytic Leukemia. Venetoclax, when combined with Obinutuzumab, has shown to significantly improve patient outcomes, such as longer progression-free survival and higher response rates, compared to traditional treatments. This combination is effective and offers a chemotherapy-free option, making it a valuable choice for patients.6791112

Research Team

AZ

Andrew Zelenetz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults diagnosed with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), who haven't had systemic therapy for these conditions, can join. They should be in a stable health condition and willing to use effective contraception. People with other active cancers, serious infections, or certain heart/liver diseases cannot participate.

Inclusion Criteria

Signed, informed consent
I have been diagnosed with CLL, SLL, or MCL according to WHO standards.
My blood counts are within normal ranges, unless affected by my condition.
See 12 more

Exclusion Criteria

Other: Females who are currently pregnant or breastfeeding, Participation in a separate investigational therapeutic study unless authorized by the investigator
Co-morbidities: Any uncontrolled illness that in the opinion of the investigator would preclude administration of study therapy, Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1, Day 1, Known bleeding diathesis, Prior major surgical procedure within 4 weeks of study, or anticipation of need for a major surgical procedure during the course of the study, Known CNS hemorrhage or stroke within 6 months of the study, History of progressive multifocal leukoencephalopathy (PML), History of HIV infection or active hepatitis B or hepatitis C infection
I haven't had any other cancers or treatments for them in the last 3 years, except for local treatments aimed at cure.
See 3 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanubrutinib and obinutuzumab starting on Cycle 1, with venetoclax added from Cycle 3, over 28-day cycles

8 months
Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRD response classification

4 weeks

Treatment Details

Interventions

  • Obinutuzumab
  • Venetoclax
  • Zanubrutinib
Trial Overview The trial is testing the combination of three drugs: Zanubrutinib, Obinutuzumab, and Venetoclax in patients with CLL/SLL. The goal is to see if this drug combo can eliminate all detectable traces of the disease from the body.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: BOVEN regimenExperimental Treatment3 Interventions
Patients will be given zanubrutinib (160mg by mouth BID) and obinutuzumab (1000mg IVPB on Days 1\*, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 through 8) starting on Cycle 1 (28-day cycles). \* On Cycle 1, obinituzumab will be administered in "split dose" at 100mg IVPB on Day 1 and 900mg IVPB on Day 2 in patients at increased risk for IRR (ALC \>25,000 cells/ul or baseline lymph nodes \>5 cm diameter). Venetoclax will be added to the regimen starting on Cycle 3, and will be incorporated into the regimen using the 5-week ramp-up schedule to mitigate the risk of tumor lysis syndrome (beginning at 20mg and gradually increasing to 400mg), and venetoclax will be administered a ta fixed dose level of 400mg by mouth daily of 28-day cycles thereafter.

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

🇺🇸
Approved in United States as Gazyva for:
  • Chronic Lymphocytic Leukemia (CLL)
  • Follicular Lymphoma
🇪🇺
Approved in European Union as Gazyva for:
  • Chronic Lymphocytic Leukemia (CLL)
  • Follicular Lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Roche-Genentech

Industry Sponsor

Trials
27
Recruited
3,800+

BeiGene USA, Inc.

Industry Sponsor

Trials
5
Recruited
490+

Massachusetts General Hospital

Collaborator

Trials
3,066
Recruited
13,430,000+

Findings from Research

The combination of rituximab and belimumab was found to be safe for patients with refractory lupus nephritis, showing no increase in adverse events compared to those receiving rituximab alone.
While the addition of belimumab did not improve clinical efficacy compared to rituximab and cyclophosphamide alone, it did lead to a greater reduction in certain B cell populations, suggesting a mechanism that enhances the negative selection of autoreactive B cells.
Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis.Atisha-Fregoso, Y., Malkiel, S., Harris, KM., et al.[2022]
In a phase III study involving 1,006 patients with active rheumatoid arthritis, treatment with ocrelizumab (both 200 mg and 500 mg doses) significantly improved symptoms and joint function compared to placebo, with ACR20 response rates of 56.9% and 54.5% at 24 weeks, respectively.
While both doses of ocrelizumab effectively reduced joint damage progression, the 500 mg dose was associated with a higher rate of serious infections compared to the 200 mg dose and placebo, indicating a need for careful monitoring of safety.
Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a forty-eight-week randomized, double-blind, placebo-controlled, parallel-group phase III trial.Rigby, W., Tony, HP., Oelke, K., et al.[2017]
In a long-term study involving 298 patients with systemic lupus erythematosus (SLE), intravenous belimumab combined with standard care showed sustained efficacy, with the percentage of patients achieving a significant response increasing from 32.8% in the first year to 75.6% by year 12.
Belimumab was well tolerated over a median treatment duration of approximately 9 years, with stable adverse event rates and maintained normal serum IgG levels, indicating its safety for long-term use in managing SLE.
Safety and Efficacy of Belimumab Plus Standard Therapy for Up to Thirteen Years in Patients With Systemic Lupus Erythematosus.Wallace, DJ., Ginzler, EM., Merrill, JT., et al.[2020]

References

Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. [2022]
Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a forty-eight-week randomized, double-blind, placebo-controlled, parallel-group phase III trial. [2017]
Safety and Efficacy of Belimumab Plus Standard Therapy for Up to Thirteen Years in Patients With Systemic Lupus Erythematosus. [2020]
Longterm clinical and immunological effects of anti-CD20 treatment in patients with refractory systemic lupus erythematosus. [2022]
Update on belimumab for the management of systemic lupus erythematosus. [2018]
Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. [2020]
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]
Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. [2022]
Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]
Venetoclax: First Global Approval. [2018]
11.United Statespubmed.ncbi.nlm.nih.gov
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]
12.United Statespubmed.ncbi.nlm.nih.gov
Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and refractory chronic lymphocytic leukemia. [2022]