The overall goal of this expanded access program is to provide Venetoclax and Navitoclax to patients with acute lymphocytic leukemia (ALL) or lymphoblastic lymphoma (LL) who have exhausted standard treatments.
Acute lymphocytic leukemia (ALL) is a cancer of the immature lymphocytes, a type of white blood cell involved in the body's immune system. People with ALL have lymphocytes that do not mature (lymphoblast). Lymphoblasts replace healthy lymphocytes within the bone marrow and other organs in the lymphatic system. Lymphoblastic lymphoma (LL) is an aggressive form of non-Hodgkin lymphoma. It is relatively rare, accounting for approximately 2% of all non-Hodgkin lymphomas. In lymphoblastic lymphoma, the abnormal lymphoblasts are present in the lymph nodes or thymus gland, whereas in ALL, the abnormal lymphoblasts are mainly in the blood and bone marrow. Clinically, lymphoblastic lymphoma behaves very similarly to ALL, and the two conditions are often treated with the same regimens. There have been several recent developments in the treatment of B-ALL, the most common cancer seen in pediatrics. While the cure rate of B-ALL is greater than 90%, children with B-ALL are treated with aggressive chemotherapy regimens that frequently result in long-term toxicities (Oeffinge, Hunger) Furthermore, the patients who experience a relapse have poor outcomes despite treatment with additional chemotherapy often followed by allogeneic stem cell transplant (AlloSCT). The primary predictor of outcome for relapsed B-ALL is the time to relapse; patients who relapse after completing chemotherapy have a cure rate of approximately 50% while those who relapse during treatment have a much lower cure rate of 20-30% (Sun). Apoptotic pathway targeting therapies, such as navitoclax show promise in the treatment of ALL and LL. Venetoclax +Navitoclax in combination with chemotherapy is well tolerated, with few discontinuations or dose reductions from adverse events (AEs) in patients with relapsed/refractory ALL or LL. The preliminary efficacy of Venetoclax +Navitoclax was promising in a heavily pretreated population of patients including those with prior SCT or CAR-T, with high rates of Complete response (CR)/complete response with incomplete count recovery (Cri)/complete response with incomplete platelet recovery (CRp), and 10/18 (56%) had undetectable minimal residual disease (MRD). Additional correlative biomarker analyses are ongoing (Pullarkat)
Study Type
EXPANDED_ACCESS
Venetoclax will be administered orally once daily (QD), continuously. Each dose of venetoclax should be taken with approximately 240 mL of water within 30 minutes after the completion of a meal, preferably breakfast. * Day 1 (200 mg equivalent): * Patients 20 \< 30 kg will take 70 mg * Patients 30 \< 35 kg will take120 mg * Patients 35 to 45 kg will take 200 mg * Day 2 onwards (400 mg equivalent): * Patients 20 \< 30 kg will take 170 mg * Patients 30 \< 35 kg will take 250 mg * Patients 35 to 45 kg will take 400 mg
Navitoclax will be administered orally once daily, starting on day 3 of cycle 1 and then may start on day 1 for subsequent cycles. Navitoclax should be taken at the same time each day approximately 24 hours apart. Dosing will be based on the recommended phase II dosing as per the phase I data and subsequent dose recommendations. * Patients 20 \< 45 kg will take 25 mg * Patients 45 kg or more will take 50 mg
University of Texas Southwestern Medical Center
Dallas, Texas, United States
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