ABT-199 & Ibrutinib in Mantle Cell Lymphoma (AIM)

Summary

This research will test the combination of two new drugs, called ibrutinib and ABT199, taken together in the treatment of Mantle Cell Lymphoma. Other studies have indicated the potential for these drugs to be used in the treatment of participants with Mantle Cell Lymphoma. In this study, the investigators will test the combination of the two drugs together, in order to determine what effects (good and bad) it has on mantle cell lymphoma. This study has two phases. The first phase is the Primary Evaluation Phase and will closely monitor the effects of ibrutinib and ABT199 for a period of 13 months. Participants who complete 13 months of treatment and continue benefiting from the study treatments will be allowed to continue both drugs until progression or intolerance in the Continuation Phase. The purpose of this phase is to provide patients with continuing access to both ibrutinib and ABT199. Patients will receive routine care from clinician, who will record any sideeffects that may be experienced. This is one of the first trials in the world to study the combination of ibrutinib and ABT199 together. Therefore the effectiveness of the combination of the study drugs will be assessed, as will how they affect mantle cell lymphoma and how it develops resistance to the treatments. The investigators also do not know whether combining the two drugs together will cause unexpected side effects. Therefore, the study will monitor patients closely and perform scans, blood tests, bone marrow biopsies and other tests at regular intervals.

Timeline

Start

2015-07-22

Primary completion

2020-11-20

Completion

2025-06

Outcome

Met primary endpoint

paper The complete response rate according to computed tomography at week 16 was 42%, which was higher than the historical result of 9% PMID 29590547 ↗

Publications

• Handunnetti SM, Khot A, Blombery P, Burbury K, Thompson PA, Ritchie D, Hicks RJ, Burke G, Koldej R, Bressel M, Di Iulio J, Westerman DA, Lade S, Roberts AW, Seymour JF, Tam CS, Anderson MA. Venetoclax and ibrutinib induces durable clinical responses in marginal zone lymphoma. Blood Adv. 2026 Mar 10;10(5):1733-1742. doi: 10.1182/bloodadvances.2025016646.
• Handunnetti SM, Anderson MA, Burbury K, Thompson PA, Burke G, Bressel M, Di Iulio J, Hicks RJ, Westerman D, Lade S, Pott C, Agarwal R, Koldej R, Ritchie D, Dreyling M, Dawson MA, Dawson SJ, Seymour JF, Roberts AW, Tam CS. Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and treatment-free remissions. Blood. 2024 Aug 22;144(8):867-872. doi: 10.1182/blood.2023023388.
• Davis JE, Handunnetti SM, Ludford-Menting M, Sharpe C, Blombery P, Anderson MA, Roberts AW, Seymour JF, Tam CS, Ritchie DS, Koldej RM. Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy. Blood Adv. 2020 Oct 13;4(19):4849-4859. doi: 10.1182/bloodadvances.2020002810.
• Tam CS, Anderson MA, Pott C, Agarwal R, Handunnetti S, Hicks RJ, Burbury K, Turner G, Di Iulio J, Bressel M, Westerman D, Lade S, Dreyling M, Dawson SJ, Dawson MA, Seymour JF, Roberts AW. Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma. N Engl J Med. 2018 Mar 29;378(13):1211-1223. doi: 10.1056/NEJMoa1715519.

Drugs

Indications