Long-Term Access to Ibrutinib and Drug Combinations for Patients with Lymphomas, Leukemias, Urothelial Carcinoma, Breast Cancer, and Graft vs Host Disease

The primary objective of this study is to provide **long-term access** to ibrutinib for subjects who continue to benefit from its use after completing previous ibrutinib clinical trials. This is clinically relevant as it allows for the continued therapeutic benefit and management of conditions such as **Chronic Lymphocytic Leukemia**, **Follicular Lymphoma**, and other specified diseases, ensuring sustained treatment efficacy and patient care.

Secondary objectives include collecting long-term safety data for subjects treated with ibrutinib and characterizing the drug's safety profile during extended treatment. This is crucial for understanding the long-term implications of ibrutinib use and ensuring patient safety over prolonged periods.

The clinical trial involves a total of **495 participants** who have previously participated in an eligible ibrutinib clinical trial. The study population includes both **male and female subjects** within the age range of **18 to 64 years**. Participants are selected based on their potential to derive clinical benefit from continued or restarted treatment with ibrutinib, as determined by their treating physician. The trial encompasses individuals with various medical conditions, including **Follicular Lymphoma**, **Chronic Lymphocytic Leukemia**, **Waldenstrom macroglobulinemia**, **Multiple Myeloma**, **Marginal Zone Lymphoma**, **Diffuse Large B-Cell Lymphoma**, **Urothelial Carcinoma**, **Breast Cancer**, **Acute Myeloid Leukemia**, **Graft vs Host Disease**, and **Mantle Cell Lymphoma**. Participants are required to have completed all assessments in their parent protocol and must not have access to commercial ibrutinib within their region. The trial includes a vulnerable population, and subjects must be willing and able to provide informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to provide long-term access to **ibrutinib** for subjects who have previously participated in eligible ibrutinib clinical trials and continue to benefit from the treatment. This is a Phase IV, non-randomized, open-label study aimed at assessing the continued efficacy and safety of ibrutinib in various conditions, including **follicular lymphoma**, **chronic lymphocytic leukemia**, **Waldenstrom macroglobulinemia**, **multiple myeloma**, **marginal zone lymphoma**, **diffuse large B-cell lymphoma**, **urothelial carcinoma**, **breast cancer**, **acute myeloid leukemia**, **graft vs host disease**, and **mantle cell lymphoma**. The trial is expected to run from March 30, 2017, to May 10, 2027, with the primary objective of allowing continued treatment with ibrutinib and drug combinations from the parent study for eligible subjects.

Participants will be involved in the study for a maximum treatment period of 120 months, with the treatment administered orally in the form of hard capsules. The study will include an initial screening visit to confirm eligibility based on the inclusion criteria, which require subjects to have completed all assessments in their parent protocol and to have no access to commercial ibrutinib within their region. Follow-up visits will be scheduled to monitor the safety and efficacy of the treatment, with assessments of treatment-emergent serious adverse events and adverse events of special interest as secondary endpoints. The end-of-study visit will conclude the participant's involvement, unless early termination is warranted due to adverse events, withdrawal of consent, or other protocol-specified conditions.

Participants are expected to adhere to the study protocol, including the use of effective birth control methods during the treatment period and for 90 days after the last dose. The study will assess the percentage of patients rolling over from each parent study as a primary endpoint. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant or their legally authorized representative. The trial is not categorized as low intervention and is conducted under the sponsorship of Pharmacyclics LLC, with ibrutinib being the primary investigational product.

The clinical trial involves the administration of **Ibrutinib**, a chemical compound, as the experimental medication. Ibrutinib is provided in the form of a hard capsule, designed for **oral use**. The maximum daily dose of Ibrutinib is 840 mg, with a total maximum dose of 3066 g over the course of the treatment period. The treatment period is capped at 120 days. The active substance in Ibrutinib is chemically synthesized and is identified by the chemical name 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo(3,4-d)pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one. The product is manufactured by Pharmacyclics LLC and is not formulated for pediatric use.

In this trial, Ibrutinib is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial's main objective is to provide long-term access to Ibrutinib for subjects who continue to benefit from it after completing previous clinical trials. Compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen. Participants are required to follow the oral administration route as per the study protocol.

Efficacy in this clinical trial will be assessed primarily through the **percentage of patients rolling over from each parent study**. This endpoint will provide insight into the continuation and potential benefits of the treatment with ibrutinib for subjects who have previously participated in eligible ibrutinib clinical trials. The secondary efficacy assessment will focus on the **number of participants with treatment emergent serious adverse events and adverse events of special interest**, as evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. These endpoints will be measured and collected throughout the trial to ensure comprehensive evaluation of the treatment's efficacy and safety profile. The trial is designed to provide long-term access to ibrutinib, allowing for continued treatment of drug combinations from the parent study for eligible subjects. The trial's estimated end date is May 10, 2027, with the recruitment having started on March 30, 2017.