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Lymphoma, Mantle-CellPhase 3NCT05431179

A Study of Zilovertamab and Ibrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma

A Phase 3 study testing Zilovertamab and Ibrutinib in people with Lymphoma, Mantle-Cell and Lymphoma, run by Oncternal Therapeutics, Inc.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a Phase 3 study to investigate the safety and efficacy of the investigational drug, zilovertamab, when given in combination with ibrutinib in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zilovertamab and Ibrutinib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Mar 2023to Dec 2026
Phase
Phase 3
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

  • Histologically confirmed MCL
  • Has received one prior regimen for MCL
  • Disease is relapsed or refractory
  • At least 1 measurable site of disease that is ≥ 2.0 cm
  • PET-CT performed less than 28 days before study entry
  • If a subject has toxicities due to prior therapy for the treatment of MCL, must be stable and recovered
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  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Study-specific laboratory parameters must be met
  • Females of childbearing potential and males must use highly effective contraception

Who cannot join

  • Received more than one month of prior therapy with ibrutinib or any other Bruton's tyrosine kinase inhibitor
  • Concurrent enrollment in another investigational study
  • Transfusion-dependent thrombocytopenia
  • Anticancer therapy within 25 days before the start of the study
  • History of other malignancy, cancer, or carcinoma for at least three years before the start of the study
  • Central nervous system (CNS) involvement with lymphoma
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  • CNS disorder ≤ 6 months of study entry
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active arrhythmias, class 3 or 4 congestive heart failure, or other clinically significant cardiac disease ≤ 6 months of study entry
  • Active or prior cardiac (atrial or ventricular) lymphoma involvement
  • History of atrial fibrillation or left or right bundle branch block
  • History of symptomatic deep vein thrombosis or pulmonary embolism ≤ 6 months of study entry
  • Chronic liver disease with hepatic impairment, Child-Pugh class B or C
  • Bleeding disorder
  • Prior stem cell transplant that requires ongoing immunosuppressive therapy or active clinical graft versus host disease
  • Primary severe immunodeficiency
  • Human immunodeficiency virus infection (HIV) or active hepatitis B or C infection
  • Active infection requiring IV antimicrobial (antiviral, antibiotic, anti-fungal) therapy at the time of study entry
  • Vaccination with a live, attenuated vaccine ≤ 4 weeks of the start of the study
  • Hypersensitivity reaction to any of the agents used in this study
  • Requires treatment with a strong cytochrome P450 enzyme (CYP) 3A (CYP3A) inhibitor/inducer.
  • Unable or swallow capsules or tablets or has malabsorption syndrome or disease affecting gastrointestinal function
  • Major surgery ≤ 4 weeks of study start
  • Medical condition likely to interfere with assessment of safety or efficacy of the study drug
  • Not eligible in the opinion of the Investigator
  • Pregnant or breastfeeding
  • Other protocol-defined inclusion/exclusion criteria will apply.

About this study

Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Zilovertamab (an ROR1 Antibody) Plus Ibrutinib Versus Ibrutinib Plus Placebo in Subjects With Relapsed or Refractory Mantle Cell Lymphoma

This is a Phase 3 study to investigate the safety and efficacy of the investigational drug, zilovertamab, when given in combination with ibrutinib in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL).

Read the detailed description

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study that will be conducted in multiple phases in patients with R/R MCL. The study phases will include a Screening Phase, an Open-Label Ibrutinib Monotherapy Treatment Phase, a Randomized Double-Blind Treatment Phase, and a Long-Term Follow-Up Phase. When patients meet all study eligibility requirements in the Screening Phase, they will enter the Open-Label Ibrutinib Monotherapy Treatment Phase and will receive ibrutinib alone daily. After approximately 16 weeks patients who have a partial response (PR) or stable disease (SD) will enter the Randomized Double-Blind Treatment Phase and will be receive an intravenous infusion of zilovertamab or placebo and will continue to receive ibrutinib daily. Patients who discontinue study drug will enter the Long-Term Follow-Up Phase.

Being tested
Zilovertamab, Ibrutinib, Placebo
Keywords
Mantle cell lymphoma, Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1), Bruton Tyrosine Kinase (BTK) inhibitor, Ibrutinib, Zilovertamab
Medical subject headings
Lymphoma, Mantle-Cell, Lymphoma, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell

What participants receive

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

  • ZilovertamabDrug

    Also called Cirmtuzumab, UC961

    After 16 weeks in the open-label Ibrutinib phase, participants will receive zilovertamab (600mg) administered by IV every 2 weeks for 3 administrations and then every 4 weeks thereafter.

  • IbrutinibDrug

    Also called Imbruvica

    All participants will receive oral Ibrutinib (560mg) daily.

  • PlaceboDrug

    After 16 weeks in the open-label Ibrutinib phase, participants will receive placebo administered by IV every 2 weeks for 3 administrations and then every 4 weeks thereafter.

Study groups in NCT05431179
Study groupRoleWhat they receive
Oral IbrutinibExperimentalOpen Label Ibrutinib Monotherapy Phase (16 weeks)
Receives: Drug: Ibrutinib
Arm A: IV Infusion of Ziloveramab and Oral IbrutinibExperimentalRandomized, Double-Blind Treatment Phase
Receives: Drug: Zilovertamab; Drug: Ibrutinib
Arm B: IV Infusion of Placebo and Oral IbrutinibPlacebo comparatorRandomized, Double-Blind Treatment Phase
Receives: Drug: Ibrutinib; Drug: Placebo

What is being measured

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

  1. Progression-free survival (PFS)

    PFS as assessed by Blinded Independent Central Review (BICR) per Lugano Classification is superior for ibrutinib plus zilovertamab compared to ibrutinib plus placebo among subjects with relapsed or refractory (R/R) mantle cell lymphoma (MCL) that had a PR or SD after 16 weeks of ibrutinib monotherapy.

    Measured: Approximately 2 years

Secondary outcomes (6)

  1. Objective Response Rate (ORR)

    Assessed by BICR per Lugano Classification, among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo.

    Measured: Approximately 4 years

  2. Duration of Response (DOR)

    Assessed by BICR per Lugano Classification, among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo.

    Measured: Approximately 4 years

  3. Complete Response Rate

    Assessed by BICR per Lugano Classification Classification among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo.

    Measured: Approximately 4 years

  4. Proportion of subjects experiencing Grade 3 to 4 neutrophil count decrease

    Proportion of subjects experiencing Grade 3 to 4 neutrophil count decrease among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo based on laboratory abnormalities.

    Measured: Approximately 4 years

  5. Overall Survival (OS)

    OS among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo.

    Measured: Approximately 4 years

  6. Overall Safety Profile

    Overall safety profile among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo. This would include incidence of treatment-emergent adverse events and laboratory abnormalities.

    Measured: Approximately 4 years

Timeline

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

  1. First posted24 Jun 2022
  2. Study startMar 2023 (estimated)
  3. Primary completionNov 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Why it stopped: Due to a strategic reprioritization based on the rapidly changing clinical and commercial landscape for Bruton's tyrosine kinase inhibitors (BTK inhibitors)

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05431179
Sponsor's protocol ID
ZILO-301
Status last verified
Apr 2023
First submitted
9 Jun 2022
Last updated
21 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.

    PubMed 25113753

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Zilovertamab and Ibrutinib in people with Lymphoma, Mantle-Cell and Lymphoma, run by Oncternal Therapeutics, Inc.

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 9 inclusion and 26 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: withdrawn, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Progression-free survival (PFS) (time frame: Approximately 2 years). 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 NCT05431179, which also lists 1 linked publication.

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 Apr 2023.

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