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Kinase inhibitor

Venetoclax + Ibrutinib + Obinutuzumab for Chronic Lymphocytic Leukemia

Phase 3

Waitlist Available

Led By Jennifer A Woyach

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 65 years

If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load

Must not have

Patients must not have any history of Richter's transformation or prolymphocytic leukemia (prolymphocytes in blood > 55%)

Patients who have had a myocardial infarction, intracranial bleed, or stroke within the past 6 months are not eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 10 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new anti-cancer drug (venetoclax) to see if it can help treat patients with chronic lymphocytic leukemia who have not received previous treatment. The drug is being added to the usual treatment of ibrutinib and obinutuzumab. The trial will also investigate whether patients who receive all three treatments and have no detectable chronic lymphocytic leukemia after one year of treatment, can stop taking ibrutinib.

Who is the study for?

This trial is for older patients (65+) with untreated chronic lymphocytic leukemia who meet specific health criteria, such as certain blood cell counts and organ function. They must not have had previous CLL treatments except for steroids or rituximab for autoimmune complications, and they should be able to swallow pills without significant gastrointestinal issues.

What is being tested?

The study tests adding Venetoclax, a BCL-2 inhibitor that may block cancer cell survival proteins, to the usual treatment of Ibrutinib and Obinutuzumab in treating CLL. It will also explore if patients can stop taking Ibrutinib after one year if no detectable CLL remains.

What are the potential side effects?

Potential side effects include risk of infection due to immune system changes, possible liver enzyme alterations leading to liver issues, fatigue, digestive problems like nausea or constipation from Venetoclax; infusion reactions from Obinutuzumab; bleeding or bruising due to low platelet count.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 65 years old or older.

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I had hepatitis C but have been treated and now have no detectable virus.

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My condition is intermediate risk with enlarged lymph nodes or liver/spleen but no anemia or low platelets.

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My CLL or SLL is at an intermediate or high-risk stage.

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My blood tests show I have a high number of B lymphocytes.

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My spleen is very large, growing, or causing symptoms.

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You have chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and meet at least one of the following criteria: anemia or low platelet count, enlarged spleen or lymph nodes, rapidly increasing lymphocyte count, autoimmune complications, or symptoms such as weight loss, fatigue, fever, or night sweats. You have completed treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL/SLL at least 4 weeks before enrollment. You must also meet certain medical requirements, including age, performance status, blood count, kidney and liver function, and ability to swallow capsules. If you have hepatitis B or C, your viral load must be undetectable, and if you have HIV, you must have undetectable viral load within the last 6 months. You must also be able to receive medication to prevent/treat tumor lysis syndrome. Additionally, you must have completed treatment through cycle 14 day 28, have central bone marrow minimal residual disease (MRD) results, and have completed response assessment with complete response determination to be eligible for re-registration.

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My lymph nodes are very large or getting worse.

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My hepatitis B is under control with undetectable viral load on treatment.

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I have been diagnosed with CLL or SLL according to the 2018 IWCLL criteria.

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I have high-risk health issues including an enlarged spleen, low hemoglobin, or low platelets not caused by autoimmune conditions.

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I have had night sweats for over a month without any infection.

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I meet the 2018 IWCLL guidelines for treatment.

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I have an autoimmune blood condition that doesn’t respond well to standard treatments.

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My cancer affects areas outside of the lymph nodes, like skin or lungs.

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I have lost 10% or more of my weight without trying in the last 6 months.

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My kidneys are functioning well enough to clear waste.

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I can swallow pills and don't have major issues with my stomach or intestines that affect food absorption.

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I am able to get out of my bed or chair and move around.

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I have had a FISH blood test for study enrollment.

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I have worsening anemia or low platelets not caused by an autoimmune condition.

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I have had a fever over 100.5°F for more than 2 weeks without an infection.

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I have been diagnosed with CLL or SLL based on my B-cell count and symptoms.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have never had Richter's transformation or prolymphocytic leukemia.

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I have not had a heart attack, brain bleed, or stroke in the last 6 months.

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I take 20 mg or less of prednisone or a similar steroid daily.

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I do not have an ongoing infection that needs IV antibiotics.

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I do not have severe heart failure, unstable chest pain, or uncontrolled irregular heartbeat.

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I am not taking strong CYP3A4/5 inhibitors, or I can stop them 14 days before the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 10 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival (PFS)

Secondary study objectives

Bone marrow (BM) minimal residual disease (MRD)- complete response (CR) rate

Incidence of adverse events

Overall survival (OS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm II (ibrutinib, obinutuzumab, venetoclax)Experimental Treatment4 Interventions

Patients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Beginning cycle 3, patients also receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. All patients will then receive a 15th cycle of ibrutinib. Beginning cycle 16, patients who do not achieve a BM MRD negative CR, receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a BM MRD negative CR undergo observation every 3 cycles for 6 years, then every 6 cycles thereafter.

Group II: Arm I (ibrutinib, obinutuzumab)Active Control2 Interventions

Patients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Treatment repeats every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 15, patients receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibrutinib

2014

Completed Phase 4

~2060

Venetoclax

2019

Completed Phase 3

~2240