Ibrutinib + Obinutuzumab for Chronic Lymphocytic Leukemia

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, CYP3A inducers

Disqualifiers: Other malignancies, Cardiovascular disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

54 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications like strong inhibitors or inducers of CYP3A, or be on systemic immunosuppressant therapy within 28 days of starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Ibrutinib and Obinutuzumab for treating chronic lymphocytic leukemia?

Research shows that Ibrutinib significantly improves survival rates in patients with chronic lymphocytic leukemia, and Obinutuzumab is approved for this condition, suggesting their combination could be effective. ^{1 2 3 4 5}

Is the combination of Ibrutinib and Obinutuzumab safe for treating chronic lymphocytic leukemia?

The combination of Ibrutinib (Imbruvica) and Obinutuzumab (Gazyva) has been studied for chronic lymphocytic leukemia and is considered safe, though some patients experienced low white blood cell counts (neutropenia) and low platelet counts (thrombocytopenia). There was one reported death due to inflammation of the small intestine (duodenitis). ^{1 3 4 6 7}

How is the drug combination of Ibrutinib and Obinutuzumab unique for treating chronic lymphocytic leukemia?

The combination of Ibrutinib and Obinutuzumab is unique because Ibrutinib is a targeted therapy that inhibits Bruton's tyrosine kinase (BTK), which is crucial for cancer cell survival, and is taken orally, while Obinutuzumab is a monoclonal antibody that helps the immune system attack cancer cells. This combination offers a novel approach by using both a targeted therapy and an immune-based treatment, potentially improving outcomes for patients with chronic lymphocytic leukemia. ^{1 5 8 9 10}

What is the purpose of this trial?

This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).

Research Team

Matthew S. Davids

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults diagnosed with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma who need treatment and have previously had therapy that didn't work. They must not be pregnant, agree to use contraception, and should not have severe allergies to monoclonal antibodies or a history of certain other cancers. Major organ functions must meet specific criteria, and they can't join if they've recently had surgery, infections requiring systemic treatment, heart issues, or are on strong CYP3A inhibitors.

Inclusion Criteria

- Progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT of <6 months.

I can do most of my daily activities without help.

My blood test results meet the study's requirements, unless my bone marrow biopsy shows significant leukemia involvement.

Exclusion Criteria

I have had cancer before, but it was a different type.

My prostate cancer is low-risk and I am being actively monitored.

I haven't taken strong immune system suppressants or more than 20 mg/day of prednisone in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib and obinutuzumab in various dosing regimens to assess safety and efficacy

6 months

Weekly visits during initial cycles, monthly visits thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for long-term efficacy and progression-free survival

2 years

Treatment Details

Interventions

• Ibrutinib
• Obinutuzumab

Trial Overview The trial is testing the effectiveness of combining two drugs: Ibrutinib and Obinutuzumab in treating Chronic Lymphocytic Leukemia (CLL). Participants will receive both medications as part of their treatment regimen to see how well they work together against CLL.

Participant Groups

Group I: Arm C- obinutuzumab/ibrutinib Experimental Treatment 2 Interventions

Participants enrolled in Arm C will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. At the same time, participants will begin to receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6.

Group II: Arm B- ibrutinib -> obinutuzumab Experimental Treatment 2 Interventions

Participants enrolled in Arm B will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. Participants will begin to receive obinutuzumab weekly starting cycle 2, and will receive obinutuzumab monthly during cycles 3-7

Group III: Arm A- obinutuzumab -> ibrutinib Experimental Treatment 2 Interventions

Participants enrolled in Arm A will receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Participants will begin to take ibrutinib daily starting cycle 2 and will continue with daily ibrutinib until the end of treatment.

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

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Obinutuzumab (Gazyva) is an effective treatment for chronic lymphocytic leukemia, targeting specific cancer cells to improve patient outcomes.

Ibrutinib (Imbruvica) is used for mantle-cell lymphoma and works by inhibiting a protein that helps cancer cells survive, while sofosbuvir (Sovaldi) effectively treats chronic hepatitis C by blocking the virus's ability to replicate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

Obinutuzumab treatment in patients with chronic lymphocytic leukemia and follicular lymphoma led to a significant decrease in natural killer (NK) cell levels in peripheral blood, dropping below the normal range.

Subcutaneous rituximab resulted in a less pronounced reduction of NK cells compared to intravenous rituximab, suggesting that the method of administration may influence NK cell levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army. García-Muñoz, R., Nájera, MJ., Feliu, J., et al.[2022]

Ibrutinib has shown high effectiveness as a first-line treatment for chronic lymphocytic leukemia in real-world settings, with 12-month overall survival rates between 95% and 96% and progression-free survival rates ranging from 89% to 93% across various studies involving 112 to 2033 patients.

The treatment demonstrated a strong response rate, with 71% to 90% of patients responding positively, and a significant majority (91% at 12 months and 87% at 24 months) did not require new treatment, indicating its sustained efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. Lee, P., Kistler, KD., Douyon, L., et al.[2023]

The combination therapy of obinutuzumab and ibrutinib, following a debulking phase with bendamustine, resulted in a 100% overall response rate in 61 patients with chronic lymphocytic leukemia (CLL), demonstrating its high efficacy.

The treatment was generally safe, with the most common severe side effects being neutropenia (14.8%) and thrombocytopenia (13.1%), and only one reported fatality, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia. von Tresckow, J., Cramer, P., Bahlo, J., et al.[2022]

References

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

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]

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

Improvement in Parameters of Hematologic and Immunologic Function and Patient Well-being in the Phase III RESONATE Study of Ibrutinib Versus Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. [2020]

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

Pharmaceutical approval update. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. [2023]

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

CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia. [2022]

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

CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Predictive significance of selected gene mutations in relapsed and refractory chronic lymphocytic leukemia patients treated with ibrutinib. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. [2022]

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

Prognostic Factors for Complete Response to Ibrutinib in Patients With Chronic Lymphocytic Leukemia: A Pooled Analysis of 2 Clinical Trials. [2021]