Ibrutinib + Obinutuzumab for Chronic Lymphocytic Leukemia

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, ibrutinib (Imbruvica) and obinutuzumab (Gazyva), to determine if they can work together to treat Chronic Lymphocytic Leukemia (CLL), a type of blood cancer. Researchers aim to assess the effectiveness of these drugs in various combinations. Individuals diagnosed with CLL who experience symptoms like significant fatigue or unintentional weight loss and have not found success with other treatments might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of ibrutinib and obinutuzumab is generally well-tolerated by patients with Chronic Lymphocytic Leukemia (CLL). One study found that patients using this combination experienced longer periods without cancer progression. While side effects occurred, they were manageable. Common issues included tiredness and nausea, but these were not severe for most individuals.

Another study found that 30 months after treatment with ibrutinib and obinutuzumab, 79% of patients had not experienced cancer progression. Some patients did encounter heart-related side effects, but these were less common. This suggests that while risks exist, many patients handle the treatment well.

Overall, evidence indicates that ibrutinib and obinutuzumab together appear safe for treating CLL, with side effects that are usually mild or manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Chronic Lymphocytic Leukemia (CLL) because they combine ibrutinib and obinutuzumab in innovative ways, potentially offering a more effective approach than current options like chemotherapy and monoclonal antibodies alone. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets cancer cells by disrupting the signals they need to survive, while obinutuzumab is an antibody that marks cancer cells for destruction by the immune system. The unique aspect of these treatments is their sequencing and combination, which could enhance their effectiveness compared to using either treatment alone. This approach might lead to better outcomes by attacking the cancer through multiple pathways simultaneously.

What evidence suggests that this trial's treatments could be effective for Chronic Lymphocytic Leukemia?

This trial will evaluate different sequences for administering ibrutinib and obinutuzumab to treat Chronic Lymphocytic Leukemia (CLL). Research has shown that combining ibrutinib with obinutuzumab can effectively treat CLL. In one study, this combination significantly extended the time patients lived without disease progression. Another study found that 92% of patients responded to ibrutinib, with 18% showing no detectable cancer. Ibrutinib is already approved for some blood cancers, supporting its use for CLL. This combination offers a promising, chemotherapy-free treatment option. ^{2 6 7 8 9}

Who Is on the Research Team?

Matthew S. Davids

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9425310/

final analysis of the randomized, phase III iLLUMINATE trial Results from the primary analysis with a median follow-up of 31 months demonstrated that ibrutinib plus obinutuzumab significantly prolonged PFS compared with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7153674/

Efficacy of Ibrutinib-Based Regimen in Chronic ... In a phase 3 trial (n = 136), the overall response rate (ORR) with ibrutinib was 92% whereas 18% patients had a complete response (CR). Progression free ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02537613

A Study of Ibrutinib + Obinutuzumab in Patients With ... This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).

4. ahdbonline.com ahdbonline.com/issues/2019/2019-payers-guide-mid-year-addendum/imbruvica-ibrutinib-plus-gazyva-obinutuzumab-first-chemotherapy-free-combination-approved-as-first-line-treatment-for-patients-with-cll-or-sll

Imbruvica (Ibrutinib) plus Gazyva (Obinutuzumab) First ... Ibrutinib was initially approved as a single agent for the treatment of other blood malignancies, including mantle-cell lymphoma, CLL or SLL with deletion 17p, ...

5. ashpublications.org ashpublications.org/bloodadvances/article/6/11/3440/484605/Up-to-8-year-follow-up-from-RESONATE-2-first-line

Up to 8-year follow-up from RESONATE-2: first-line ibrutinib ... Long-term RESONATE-2 data show sustained PFS and OS benefits (medians not reached) for first-line ibrutinib treatment in patients with CLL.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11971162/

Final results on effectiveness and safety of Ibrutinib in patients ... We conducted an observational study (FIRE) to understand the effectiveness and safety outcomes of ibrutinib in patients with chronic lymphocytic leukemia (CLL) ...

7. haematologica.org haematologica.org/article/view/haematol.2021.279012

final analysis of the randomized, phase III iLLUMINATE trial Ibrutinib plus obinutuzumab showed sustained clinical benefit, in terms of progression- free survival, in first-line treatment of chronic lymphocytic leukemia.

8. nature.com nature.com/articles/s41375-021-01485-x

Efficacy and safety in a 4-year follow-up of the ELEVATE ... In that study, median PFS (assessed by IRC) was not reached; the estimated 30-month PFS rate was 79% with ibrutinib-obinutuzumab. Atrial ...

9. ashpublications.org ashpublications.org/bloodadvances/article/9/10/2431/536217/Long-term-outcomes-of-chemoimmunotherapy-with

Long-term outcomes of chemoimmunotherapy with ... In CLL11 and in a more recent study (CLL13), obinutuzumab achieved higher rates of undetectable minimal residual disease compared with rituximab when combined ...