A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (>/= 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)
New drug combination tested for older adults with untreated chronic lymphocytic leukemia
Plain English Summary
Testing the Addition of a New Anti-cancer Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Obinutuzumab) in Untreated, Older Patients With Chronic Lymphocytic Leukemia is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma. This study tests if adding a new cancer drug, venetoclax, to the standard treatment (ibrutinib and obinutuzumab) is more effective for older patients with chronic lymphocytic leukemia (CLL) who haven't been treated before. It is for patients aged 65 and older who have been diagnosed with CLL or SLL and meet specific criteria for treatment. Participation involves receiving one of two treatment combinations and regular medical check-ups. Some patients may be able to stop ibrutinib after a year if their leukemia is undetectable. Alternative treatments for CLL include other chemotherapy drugs, targeted therapies, and stem cell transplants, depending on the individual's condition and treatment history. The trial aims to enroll 465 participants.
Official Summary
This phase III trial compares adding a new anti-cancer drug (venetoclax) to the usual treatment (ibrutinib plus obinutuzumab) in older patients with chronic lymphocytic leukemia who have not received previous treatment. The addition of venetoclax to the usual treatment might prevent chronic lymphocytic leukemia from returning. This trial also will investigate whether patients who receive ibrutinib plus obinutuzumab plus venetoclax and have no detectable chronic lymphocytic leukemia after 1 year of treatment, can stop taking ibrutinib. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving ibrutinib and obinutuzumab with venetoclax may work better at treating chronic lymphocytic leukemia compared to ibrutinib and obinutuzumab.
Who Can Participate
Here is what you need to know about eligibility for this trial. Patients must be 65 years or older and have a diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The leukemia must require treatment based on specific guidelines, such as significant symptoms, bone marrow failure, or rapidly progressing disease. Patients cannot have received prior treatment for their CLL/SLL, with some exceptions for prior treatment of autoimmune complications. Good general health is required, including adequate blood counts, kidney, and liver function, and the ability to swallow pills. This trial is studying Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, so participants generally need a confirmed diagnosis.
What They're Measuring
The primary outcome, progression-free survival, measures how long patients live without their cancer getting worse, indicating how well the new drug combination controls the leukemia. The specific primary outcome measures are: Progression-free Survival (PFS) (5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.
Why This Trial Matters
This trial addresses a need for more effective and potentially less toxic treatment options for older adults newly diagnosed with chronic lymphocytic leukemia, aiming to improve long-term outcomes. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, where improved treatment options are needed.
Investor Insight
This trial is sponsored by the National Cancer Institute, suggesting a focus on advancing treatment for a significant cancer. The study design and enrollment target indicate a robust investigation int Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.
Is This Trial Right for Me?
Ask your doctor about the specific treatments being tested, potential side effects of each drug, and how participation might affect your daily life. Be prepared for regular clinic visits for treatment administration, blood tests, and monitoring of your health and cancer status. Understand that you will be randomly assigned to one of the treatment groups, and your doctor will discuss the assigned treatment with you. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: RANDOMIZED
- Model: PARALLEL
- Masking: NONE
- Enrollment: 465 participants
Interventions
- DRUG: Ibrutinib — Given PO
- BIOLOGICAL: Obinutuzumab — Given IV
- OTHER: Observation Activity — Undergo observation
- DRUG: Venetoclax — Given PO
Primary Outcomes
- Progression-free Survival (PFS) (5 years)
Secondary Outcomes
- Bone Marrow (BM) Minimal Residual Disease (MRD)- Complete Response (CR) Rate (Up to 10 years)
- Overall Survival (OS) (From randomization date until death from any cause, assessed up to 10 years)
- Incidence of Adverse Events (Up to 10 years)
Full Eligibility Criteria
Inclusion Criteria:
* PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)
* Patients must have been diagnosed with chronic lymphocytic leukemia (CLL) (\> 5000 B-cells per uL of peripheral blood at any point during the course of their disease) or small lymphocytic lymphoma (SLL) with \< 5000 B-cells per uL of blood but with disease-associated lymphadenopathy
* This blood submission is mandatory prior to registration/randomization to perform fluorescence in situ hybridization (FISH) centrally that will be used for stratification. It should be obtained as soon after pre-registration as possible
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1)
* Patients must be diagnosed with CLL or SLL in accordance with 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria that includes all of the following:
* \>= 5 x10\^9 B lymphocytes (5000/uL) in the peripheral blood measured by flow cytometry at any point in the course of the disease or less peripheral blood involvement but disease-associated lymphadenopathy
* On local morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes
* Neoplastic cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression or lack of CD23 expression in \>10% of cells must lack t(11;14) translocation by interphase cytogenetics
* Patients must be intermediate or high-risk Rai stage CLL or SLL
* Intermediate risk (formerly stage I/II) is defined by lymphadenopathy and/or hepatomegaly or splenomegaly without anemia or thrombocytopenia
* High risk (formerly stage III/IV) is defined by splenomegaly and/or anemia (hemoglobin \< 11g/dL) not attributable to autoimmune hemolytic anemia and/or thrombocytopenia (platelets \[plt\] \< 100 x10\^9/L) not attributable to autoimmune thrombocytopenia
* Patients must meet criteria for treatment as defined by 2018 IWCLL guidelines which includes at least one of the following criteria:
* Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
* Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
* Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy
* Progressive lymphocytosis with a lymphocyte doubling time \< 6 months or an increase of \>= 50% over a 2 month period
* Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
* Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)
* Constitutional symptoms, which include any of the following:
* Unintentional weight loss of 10% or more within 6 months
* Significant fatigue
* Fevers \> 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
* Night sweats \>= 1 month without evidence of infection
* Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL/SLL must be complete at least 4 weeks prior to enrollment. Palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
* Age \>= 65 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3 except if due to bone marrow involvement
* Platelet count (untransfused) \>= 30,000/mm\^3 except if due to bone marrow involvement
* Calculated (Calc.) creatinine clearance \>= 40 mL/min (by Cockcroft-Gault)
* Bilirubin =\< 1.5 x upper limit of normal (ULN) except if due to liver involvement, hemolysis, or Gilbert's disease
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) except if due to liver involvement
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* Please note: Intravenous immunoglobulin therapy (IVIG) can cause a false positive hepatitis B serology. If patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B deoxyribonucleic acid \[DNA\]) they may still participate in the study, must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Central fluorescent in situ hybridization (FISH) blood results are mandatory prior to registration/randomization for it will be used for stratification
* Patients must be able to swallow capsules and noTrial Locations
- University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
- Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
- Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
- Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
- Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
- Alaska Women's Cancer Care, Anchorage, Alaska, United States
- Anchorage Oncology Centre, Anchorage, Alaska, United States
- Katmai Oncology Group, Anchorage, Alaska, United States
- Providence Alaska Medical Center, Anchorage, Alaska, United States
- Fairbanks Memorial Hospital, Fairbanks, Alaska, United States
- ...and 10 more locations
Frequently Asked Questions
What is clinical trial NCT03737981?
NCT03737981 is a Phase 3 INTERVENTIONAL study titled "Testing the Addition of a New Anti-cancer Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Obinutuzumab) in Untreated, Older Patients With Chronic Lymphocytic Leukemia." It is currently active, not recruiting and is sponsored by National Cancer Institute (NCI). The trial targets enrollment of 465 participants.
What conditions does NCT03737981 study?
This trial investigates treatments for Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma. The primary condition under study is Chronic Lymphocytic Leukemia.
What treatments are being tested in NCT03737981?
The interventions being studied include: Ibrutinib (DRUG), Obinutuzumab (BIOLOGICAL), Observation Activity (OTHER), Venetoclax (DRUG). Given PO
What does Phase 3 mean for NCT03737981?
Phase 3 trials are large-scale studies involving 300-3,000+ patients that compare the new treatment against existing standard treatments. Positive Phase 3 results are typically required for FDA approval.
What is the current status of NCT03737981?
This trial is currently "Active, Not Recruiting." It started on 2019-01-31. The estimated completion date is 2026-12-29.
Who is sponsoring NCT03737981?
NCT03737981 is sponsored by National Cancer Institute (NCI). The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT03737981?
The trial aims to enroll 465 participants. The trial status is active, not recruiting.
How is NCT03737981 designed?
This is a interventional study, uses randomized allocation, follows a parallel design, employs none masking.
What are the primary outcomes being measured in NCT03737981?
The primary outcome measures are: Progression-free Survival (PFS) (5 years). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT03737981 being conducted?
This trial is being conducted at 20 sites, including Birmingham, Alabama; Anchorage, Alaska; Fairbanks, Alaska; Kingman, Arizona and 16 more sites (United States).
Where can I find official information about NCT03737981?
The official record for NCT03737981 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT03737981. This government database provides the most up-to-date and detailed information about the trial.
What is NCT03737981 testing in simple terms?
This study tests if adding a new cancer drug, venetoclax, to the standard treatment (ibrutinib and obinutuzumab) is more effective for older patients with chronic lymphocytic leukemia (CLL) who haven't been treated before. It is for patients aged 65 and older who have been diagnosed with CLL or SLL and meet specific criteria for treatment.
Why is this trial significant?
This trial addresses a need for more effective and potentially less toxic treatment options for older adults newly diagnosed with chronic lymphocytic leukemia, aiming to improve long-term outcomes. As a Phase 3 trial, positive results could lead directly to regulatory approval and new treatment options for patients.
What are the potential risks of participating in NCT03737981?
Common side effects of ibrutinib can include diarrhea, fatigue, and bruising. Obinutuzumab can cause infusion-related reactions like fever and chills. Venetoclax may cause low white blood cell counts, increasing infection risk, and can lead to tumor lysis syndrome, a rapid breakdown of cancer cells, which requires careful monitoring. Other potential risks include increased risk of infections, heart problems, and bleeding. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT03737981?
Ask your doctor about the specific treatments being tested, potential side effects of each drug, and how participation might affect your daily life. Be prepared for regular clinic visits for treatment administration, blood tests, and monitoring of your health and cancer status. Understand that you will be randomly assigned to one of the treatment groups, and your doctor will discuss the assigned treatment with you. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT03737981 signal from an investment perspective?
This trial is sponsored by the National Cancer Institute, suggesting a focus on advancing treatment for a significant cancer. The study design and enrollment target indicate a robust investigation int This is a Phase 3 trial, which is the final pivotal stage before potential regulatory submission.
What happens if the treatment in this trial doesn't work?
Participation involves receiving one of two treatment combinations and regular medical check-ups. Some patients may be able to stop ibrutinib after a year if their leukemia is undetectable. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.