Venetoclax Clinical Trials

What Is Venetoclax?

Venetoclax is an FDA-approved medication for certain adult patients with Acute Myeloid Leukemia (AML) and Chronic Lymphocytic Leukemia (CLL). It is an oral drug that works by blocking a protein called BCL-2. BCL-2 helps cancer cells survive, so by inhibiting this protein, venetoclax can lead to the death of cancer cells.

In addition to its approved uses, venetoclax is being investigated in clinical trials for a variety of other blood cancers and solid tumors. These studies aim to evaluate its safety and effectiveness, often in combination with other therapies, for conditions such as myelodysplastic syndromes, various lymphomas, and multiple myeloma.

Uses and Conditions Under Study

Venetoclax is extensively studied across a broad range of cancers, primarily hematological malignancies. There are 686 trials involving venetoclax, with 259 currently recruiting participants and 115 completed. A total of 79,552 participants have been enrolled in studies involving venetoclax since the first trial began in 2007.

• Acute Myeloid Leukemia (AML) and related conditions: Venetoclax is FDA-approved for certain AML patients, particularly those aged 75 or older or with comorbidities that prevent intensive chemotherapy. It is being studied in 171 trials for Acute Myeloid Leukemia, 39 trials for Refractory Acute Myeloid Leukemia, 36 trials for Recurrent Acute Myeloid Leukemia, and 26 trials for Myeloid Leukemia, Acute. These trials explore venetoclax as a monotherapy or in combination with other agents, including in newly diagnosed, relapsed, or refractory settings.
• Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): Venetoclax is FDA-approved for adult patients with CLL. It is being investigated in 63 trials for Chronic Lymphocytic Leukemia and 33 trials for Small Lymphocytic Lymphoma. Studies evaluate its use in previously treated patients, as a first-line therapy, and in combination with other targeted agents or immunotherapies.
• Myelodysplastic Syndromes (MDS): This group of conditions involves problems with blood cell production in the bone marrow. Venetoclax is being studied in 26 trials for Myelodysplastic Syndromes and 23 trials for Myelodysplastic Syndrome, often in combination with hypomethylating agents, to improve outcomes for patients, especially those with intermediate or high-risk disease.
• Lymphomas: Venetoclax is being explored for various types of lymphoma, including Non-Hodgkin Lymphoma (NHL), Mantle Cell Lymphoma (MCL), Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), and Marginal Zone Lymphoma (MZL). These trials investigate venetoclax alone or in combination with chemotherapy or other targeted therapies to target BCL-2 overexpression common in these cancers.
• Other Cancers: Venetoclax is also under investigation for other hematological malignancies like Multiple Myeloma and Waldenström's Macroglobulinemia, as well as solid tumors such as Non-Small Cell Lung Cancer and metastatic colorectal cancer. These studies aim to determine if venetoclax can enhance the effects of existing treatments or provide new options.

Additionally, some studies involve venetoclax to assess its pharmacokinetics in specific populations, such as female participants receiving ethinyl estradiol and levonorgestrel.

Dosing

Venetoclax is primarily administered orally, often as a tablet. While most studies involve oral administration, some trials have explored intravenous (IV) delivery.

The dosage of venetoclax can vary significantly depending on the condition being treated and whether it is used alone or in combination with other medications. Common oral doses studied range from 70 mg to 1200 mg daily. A frequently studied dose is 400 mg once daily, often following a ramp-up schedule where the dose is gradually increased over several days or weeks to help manage potential side effects.

Examples of dosing regimens include:

• 80 mg once daily orally for 28 days in initial cycles, sometimes followed by other agents.
• A ramp-up schedule starting with 100 mg on day 1, 200 mg on day 2, and then 400 mg on days 3-28, particularly when combined with azacitidine.
• Doses of 200 mg, 300 mg, 600 mg, 800 mg, 900 mg, or 1200 mg have been investigated in various phase 1 and phase 2 studies to determine optimal safety and efficacy.

Venetoclax is frequently studied in combination therapies, where its dose and schedule are adjusted to complement other drugs, such as azacitidine, decitabine, rituximab, ibrutinib, or various chemotherapy regimens. It is being studied in both adult and pediatric patients with acute myeloid leukemia, with specific regimens tailored to each population.

Side Effects

In clinical trials, patients taking Venetoclax experienced various side effects. The most common side effect was diarrhea, affecting 47.5% of patients on Venetoclax compared to 35.1% on placebo. Nausea was reported by 39.3% of patients on Venetoclax versus 26.6% on placebo. Neutropenia, a decrease in a type of white blood cell, occurred in 36.1% of patients receiving Venetoclax, compared to 17.7% on placebo. Other common side effects included:

• Thrombocytopenia (low platelet count): 31.9% on Venetoclax vs 30.9% on placebo
• Constipation: 30.4% on Venetoclax vs 29.3% on placebo
• Anemia (low red blood cell count): 28.7% on Venetoclax vs 22.8% on placebo
• Fatigue: 26.0% on Venetoclax vs 23.0% on placebo
• Vomiting: 25.4% on Venetoclax vs 16.8% on placebo
• Hypokalaemia (low potassium levels): 24.6% on Venetoclax vs 17.3% on placebo
• Decreased appetite:

  Currently Recruiting Trials

  Many clinical trials are currently recruiting participants to explore new ways to use venetoclax, a medication that targets the BCL-2 protein, in treating various cancers and other conditions. These studies investigate venetoclax both as a standalone therapy and in combination with other agents, aiming to improve treatment outcomes.

  • One significant study, NCT06917911, is a Phase 2 trial sponsored by the National Cancer Institute. It is enrolling up to 162 participants with core binding factor acute myeloid leukemia (CBF-AML) to compare venetoclax combined with cytarabine and daunorubicin ("7+3" regimen) against gemtuzumab ozogamicin with the same "7+3" regimen.
  • For patients with relapsed or refractory CD19 positive B-cell acute lymphoblastic leukemia, the City of Hope Medical Center is sponsoring a Phase 1 trial (NCT07133997) with an enrollment target of 26 individuals. This study evaluates the safety and effectiveness of recombinant Erwinia asparaginase and venetoclax in combination with blinatumomab.
  • A large Phase 3 study, NCT07277231, sponsored by BeOne Medicines, is recruiting up to 500 participants with previously untreated chronic lymphocytic leukemia (CLL). It compares a fixed-duration combination of sonrotoclax and zanubrutinib against venetoclax plus acalabrutinib.
  • AbbVie is sponsoring NCT07387471, a Phase 2 trial for 14 adult participants with relapsed or refractory Waldenström macroglobulinemia (WM) or lymphoplasmacytic lymphoma (LPL). This study assesses the change in disease activity with venetoclax monotherapy.
  • Beyond cancer, venetoclax is being explored in other areas, such as HIV-1 infection. Thomas Aagaard Rasmussen is sponsoring a Phase 1 study (NCT07481175) with 38 participants to investigate venetoclax concurrent with initiating antiretroviral therapy (ART) to promote apoptosis of HIV-infected cells and restrict the seeding of the HIV reservoir.
  • Another notable Phase 3 trial, NCT07007312, sponsored by Kura Oncology, Inc., is enrolling a substantial 1300 patients with untreated NPM1-mutated or KMT2A-rearranged acute myeloid leukemia (AML). This study investigates ziftomenib in combination with venetoclax and azacitidine, or with the "7+3" regimen.

  These are just a few examples among the many ongoing studies, which collectively involve thousands of patients exploring the potential of venetoclax for a wide range of conditions.

  Where to Participate

  Clinical trials involving venetoclax are widely accessible, with studies taking place across many countries and US states. There are currently 1407 sites in 590 cities and 51 states actively recruiting participants. This broad geographic reach helps ensure diverse patient populations can contribute to research efforts.

  The top ten cities with the most recruiting sites include:

  • Houston, Texas (60 sites)
  • Boston, Massachusetts (58 sites)
  • New York, New York (57 sites)
  • Columbus, Ohio (37 sites)
  • St Louis, Missouri (35 sites)
  • Chicago, Illinois (33 sites)
  • Seattle, Washington (32 sites)
  • Portland, Oregon (29 sites)
  • Flint, Michigan (27 sites)
  • Philadelphia, Pennsylvania (26 sites)

  Eligibility for these trials is generally broad, welcoming participants of all genders. The age range for participation spans from 1 to 365 years, and many studies include children and healthy volunteers, depending on the specific research goals.

  Development Timeline

  The journey of venetoclax in clinical development began on July 16, 2007, with the latest trial initiated on May 26, 2026. Since its inception, venetoclax has been investigated in a total of 686 trials, enrolling over 79,552 participants worldwide. This extensive research pipeline reflects a significant commitment to understanding and expanding the therapeutic applications of this medication.

  Development has progressed through all phases, with a strong emphasis on Phase 2 (269 trials) and Phase 1 (158 trials) studies, alongside numerous Phase 1/Phase 2 (125 trials) and Phase 3 (59 trials) investigations. Key sponsors driving this research include institutions like the M.D. Anderson Cancer Center (69 trials), AbbVie (56 trials), and the National Cancer Institute (34 trials), among many others globally.

  Initially, venetoclax, a BCL-2 inhibitor, focused on hematologic malignancies such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Over time, its pipeline has expanded significantly to include a wide array of conditions, including various lymphomas like mantle cell lymphoma and marginal zone lymphoma, multiple myeloma, and myelodysplastic syndromes. More recently, its potential is being explored in non-cancer indications, such as HIV-1 infection, demonstrating the drug's versatile mechanism of action and the ongoing efforts to discover new therapeutic benefits.