AzTrials
AzTrials

Mantle Cell LymphomaPhase 2AIMNCT02471391

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

A Phase 2 study testing ABT-199 and Ibrutinib in people with Mantle Cell Lymphoma, run by Peter MacCallum Cancer Centre, Australia at 2 sites in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
ABT-199 and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
2 sitesAustralia
Study dates
22 Jul 2015to Jun 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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);
Show all 21Show fewer
  • 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);
  • Double-barrier method (contraceptive sponge, diaphragm or cervical cap with spermicidal jellies or cream AND a condom);
  • Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration.
  • Female subjects of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [B-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Male subjects must agree to refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug.
  • Subject is able to swallow whole tablets.
  • Subject (or their legally-acceptable representatives) must sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.

Who cannot join

  • 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.
Show all 31Show fewer
  • 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),
  • Antiretroviral medications.
  • Subject has consumed the following within 3 days prior to the first dose of study drug.
  • Grapefruit, or
  • Grapefruit products, or
  • Seville oranges (including marmalade containing Seville oranges), or
  • Star fruit
  • Subject has clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
  • Subject has a life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
  • •specifically, a subject with history of stroke or intracranial hemorrhage within 6 months prior to enrollment is excluded
  • Subject has a history of other active malignancies other than MCL within the past 2 years prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the cervix uteri,
  • Adequately treated basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Subject has known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
  • Received live, attenuated vaccines within 4 weeks of first dose of ibrutinib
  • Major surgery within 4 weeks of first dose of ibrutinib

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

  • Peter MacCallum Cancer Centre

    East Melbourne, Victoria, 3002

  • Royal Melbourne Hospital

    Melbourne, Victoria, 3000

Other trials in Australia

About this study

Official title: A Phase 2 Study of ABT-199 in Combination With Ibrutinib in the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma (AIM Study)

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.

Being tested
ABT-199, Ibrutinib
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02471391
Study groupRoleWhat they receive
Ibrutinib + ABT-199ExperimentalNot described
Receives: Drug: ABT-199; Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete response measured using IWG at 16 weeks

    Measured: Measured at 16 weeks after commencement of treatment.

Secondary outcomes (9)

  1. Completing 4, 16, 28, 40 and 56 weeks of treatment

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

  2. Toxicities measured using CTCAE version 4

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

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

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

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

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

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

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

  6. Progression free survival

    Measured: From start of treatment until the date of first documented progression or date of death from any cause, whichever occures first, assessed up to the date when the last patient has their 13 months assessment.

  7. Overall survival

    Measured: From start of treatment until the date of death from any cause assessed up to the date when the last patient has their 13 months assessment.

  8. Duration of response

    Measured: From first disease response date to the date of earliest recurrance or PD, assessed up to the date when the last patient has their 13 months assessment.

  9. Time to progression

    Measured: From start of treatment until the date of first documented progression assessed up to the date when the last patient has their 13 months assessment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2015 (estimated)
  2. Study start22 Jul 2015
  3. Primary completion20 Nov 2020
  4. Study completionJun 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02471391
Sponsor's protocol ID
14/148
Acronym
AIM
Status last verified
Aug 2023
First submitted
12 May 2015
Last updated
21 Aug 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • Davis JE, Le LHH, Ludford-Menting M, Holzwart N, Handunnetti SM, Tam CS, Anderson MA, Ritchie DS, Koldej RM. Marginal zone lymphoma is associated with dysregulated T-cell immunity that is not altered by ibrutinib-venetoclax treatment. Blood Neoplasia. 2026 Jun 25;3(3):100260. doi: 10.1016/j.bneo.2026.100260. eCollection 2026 Aug.

    PubMed 42540369

  • 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.

    PubMed 41380113

  • 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.

    PubMed 38662991

  • 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.

    PubMed 33031542

  • 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.

    PubMed 29590547

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ABT-199 and Ibrutinib in people with Mantle Cell Lymphoma, run by Peter MacCallum Cancer Centre, Australia at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete response measured using IWG at 16 weeks (time frame: Measured at 16 weeks after commencement of treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02471391, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in