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

NCT02471391 | Unknown Phase 2 DMC

• 1 other identifier: 14/148
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete response measured using IWG at 16 weeks

  Measured at 16 weeks after commencement of treatment.

Secondary Outcomes (9)

• Completing 4, 16, 28, 40 and 56 weeks of treatment

  Assessed at 4, 16, 28, 40 and 56 weeks

• Toxicities measured using CTCAE version 4

  Continuously measured while on treatment up to a maximum of 56 weeks

• Overall response (CR + PR) using IWG criteria at 4, 16, 28, 40 and 56 weeks

  Assessed at 4, 16, 28, 40 and 56 weeks

• Complete response using IWG criteria at 4, 16, 28, 40 and 56 weeks

  Assessed at 4, 16, 28, 40 and 56 weeks

• Minimal residual disease (MRD) at 4, 16, 28, 40 and 56 weeks

  Assessed at 4, 16, 28, 40 and 56 weeks

Study Arms (1)

Ibrutinib + ABT-199

EXPERIMENTAL

Drug: ABT-199; Drug: Ibrutinib

Interventions

ABT-199 DRUG

Ibrutinib + ABT-199

Ibrutinib DRUG

Ibrutinib + ABT-199

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be \>/= 18 years of age.
• Subject must have a confirmed diagnosis of Mantle Cell Lymphoma (MCL) according to WHO (2008) criteria, and have received at least one prior line of systemic therapy for MCL.
• Subject requires treatment in the opinion of the investigator, and has at least one site of radiographically assessable disease not previously irradiated (lymph node with largest diameter \>/= 1.5cm, or unequivocal hepatomegaly / splenomegaly)
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of \</= 2.
• Subject must have adequate bone marrow function at Screening as follows:
• Absolute Neutrophil Count (ANC) \>/= 1.0 x 109/L (neutropenia due to marrow infiltration may be supported by growth factors);
• Platelets \>/= 50 x 109/L (entry platelet count must be independent of transfusion within 7 days).
• Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:
• aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN);
• Serum creatinine not to exceed 2 x ULN, and a calculated creatinine clearance of at least 50 mL/min using the Cockcroft-Gault equation or a 24-hour urine collection;
• AST or ALT \</= 3.0 × the upper normal limit (ULN) of institution's normal range; Bilirubin \</= 1.5 × ULN. Subjects with documented Gilbert's Syndrome may have a bilirubin \> 1.5 × ULN.
• Female subjects of childbearing potential and non-sterile male subjects (with partners of child bearing potential) must practice at least one of the following methods of birth control with partner(s) from initial study drug administration to 90 days after the last dose of study drug:
• Total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable;
• Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy;
• Intrauterine device (IUD);

You may not qualify if:

• Subject has undergone an allogeneic stem cell transplant within the last 6 months or currently has active graft-vs-host disease requiring the use of immunosuppressants.
• Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP).
• Subject has known central nervous system involvement by MCL.
• Subject previously participated in an ibrutinib clinical trial or subject previously received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib
• Subject has received the following within 30 days prior to the first dose of study drug:
• Monoclonal antibody given with anti-neoplastic intent.
• Subject has received any of the following within 14 days prior to the first dose of study drug, or has not recovered to less than CTC grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
• Any anti-cancer therapy including chemotherapy, or radiotherapy;
• Investigational therapy, including targeted small molecule agents.
• Subject has received the following within 7 days prior to the first dose of study drug:
• Steroid therapy given with anti-neoplastic intent
• Subjects requires ongoing therapy with:
• Potent CYP3A inhibitors (such as indinavir, ketoconazole, and clarithromycin),
• Potent CYP3A inducers (e.g., rifampin, phenytoin, carbamazepine or St. John's Wort),
• Warfarin, or or equivalent vitamin K antagonist (eg, phenprocoumon),

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (2)

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3000, Australia

Location

Related Publications (4)

• Handunnetti SM, Khot A, Blombery P, Burbury K, Thompson PA, Ritchie D, Hicks RJ, Burke G, Koldej RM, Bressel M, Di Iulio JL, 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. 2025 Dec 11:bloodadvances.2025016646. doi: 10.1182/bloodadvances.2025016646. Online ahead of print.

  PMID: 41380113 DERIVED

• 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.

  PMID: 38662991 DERIVED

• 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.

  PMID: 33031542 DERIVED

• 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.

  PMID: 29590547 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

venetoclax; ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: June 15, 2015
• Study Start: July 22, 2015
• Primary Completion: November 20, 2020
• Study Completion: June 1, 2025
• Last Updated: August 21, 2023

Record last verified: 2023-08

Locations

AU (2)