In short
Clinical trials investigating Venetoclax are studying how well it works in different diseases, along with safety and tolerability. These trials include patients with leukemia, lymphoma, multiple myeloma, and some other conditions, in both newly diagnosed and relapsed or refractory settings. Many studies compare Venetoclax combinations with other treatments or standard care.
Key points
- Clinical trials investigating Venetoclax are testing it in many blood cancers, especially AML, CLL, SLL, mantle cell lymphoma, and multiple myeloma. The studies include both newly diagnosed patients and people with relapsed or refractory disease, meaning the cancer came back or did not respond to earlier treatment. Most trials study Venetoclax in combinations with other drugs and compare outcomes such as survival, response rate, and minimal residual disease. The trial phases range from early dose-finding studies to large Phase 3 comparisons. Some studies are also looking at special groups, such as older patients, people with genetic changes, or patients who are not fit for intensive chemotherapy.
Overview of Venetoclax trials
These clinical trials study Venetoclax in many cancer settings and in a few other diseases. Most studies test Venetoclax as part of a combination, not as a single treatment. The main goals are to learn about safety, tolerability, and how well the treatment works in specific patient groups.
The trial data show a wide range of study sizes, from small early studies to large Phase 3 trials with hundreds of patients. Some studies are completed, while others are authorised or suspended.
Conditions being studied
Many trials focus on acute myeloid leukemia (AML), including newly diagnosed AML, relapsed or refractory AML, and AML with specific genetic changes such as NPM1, KMT2A, FLT3, IDH1, or RARA-related disease. Several studies also include chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), including first-line, relapsed, and high-risk disease.
Other blood cancers in the trial set include mantle cell lymphoma, multiple myeloma, Waldenström’s macroglobulinemia, chronic myelomonocytic leukemia (CMML), and myelodysplastic syndrome (MDS). There are also studies in blastic plasmacytoid dendritic cell neoplasm, Richter syndrome, and acute graft-versus-host disease of the skin.
A few trials look beyond cancer, including studies in HIV-1 disease and HIV-1 infection, where the aim is to study safety and effects on the HIV reservoir, which means the hidden pool of virus in the body.
Trial designs and phases
The trials include Phase 1, Phase 2, Phase 3, and some Phase 4 studies. Phase 1 studies mainly check safety, dose limits, and the recommended dose for later testing. Phase 2 studies often look at early signs of benefit, such as remission or MRD negativity.
Phase 3 studies are larger and usually compare Venetoclax combinations with another treatment, placebo, or standard care. Some studies are open-label, which means both the researchers and participants know which treatment is being given. Other studies are randomized, meaning patients are assigned by chance to different treatment groups.
Main endpoints being measured
The most common endpoints are overall survival (OS), progression-free survival (PFS), event-free survival (EFS), and response rates such as overall response rate (ORR) or complete remission (CR). These endpoints help show whether a treatment helps people live longer, stay well longer, or have a better cancer response.
Many trials also use minimal residual disease (MRD) or undetectable MRD (uMRD) as important endpoints. MRD testing looks for very small amounts of cancer that may remain after treatment, even when the patient seems to be in remission. Some studies also measure dose-limiting toxicities, adverse events, and pharmacokinetics, which is how the body handles a treatment.
Who may be able to participate
Eligibility depends on the trial and the disease being studied. Some studies are for people who have never been treated before, while others are for people whose cancer has returned or did not respond to earlier therapy.
Several studies focus on special groups, such as older adults, people who are not fit for intensive chemotherapy, patients with specific genetic changes, or patients who already reached remission but still have MRD. Some trials also look at people after stem cell transplantation or after previous Venetoclax treatment.
Important trial examples
NCT02993523 studied Venetoclax plus azacitidine versus azacitidine alone in previously untreated AML, with outcomes of CR/CRi and overall survival. NCT03069352 tested Venetoclax with low-dose cytarabine in untreated AML patients who were not eligible for intensive chemotherapy, with overall survival as the main endpoint.
NCT04608318, NCT06073821, and NCT05057494 are large Phase 3 studies in previously untreated CLL or CLL/SLL that compare Venetoclax-based regimens with other treatment approaches and measure PFS. NCT06943872 and NCT04965493 study relapsed or refractory CLL/SLL and compare Venetoclax-based retreatment or combinations against other options using PFS or response-based outcomes.
NCT02899052 and NCT03539744 focus on multiple myeloma, especially t(11;14)-positive disease, and measure response rates and PFS. NCT05099471 studies Venetoclax with rituximab in Waldenström’s macroglobulinemia and looks at complete or very good partial remission rates.
NCT04581512, NCT06156579, NCT04763928, and NCT05431257 are examples of AML and related myeloid disorder studies that test Venetoclax with other agents and measure remission, EFS, or response rates. NCT05807932 and NCT2025-521372-62-00 study Venetoclax around allogeneic stem cell transplantation and measure safety or survival after transplant.
Patient-friendly explanation of key terms
Combination therapy means Venetoclax is given with one or more other drugs in the same study. Maintenance therapy means treatment given after the main treatment phase to help keep the disease under control.
Relapsed means the disease came back after treatment, and refractory means it did not respond well to treatment. Randomized means patients are assigned by chance to different study groups, which helps compare treatments fairly.
Open-label means the treatment is known to everyone in the study. Blinded independent review or central review means outside experts check the results in a standard way, which helps reduce bias.