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

April 19, 2023 updated by: Oncternal Therapeutics, Inc

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).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Ibrutinib
Open Label Ibrutinib Monotherapy Phase (16 weeks)
Drug: Ibrutinib
All participants will receive oral Ibrutinib (560mg) daily.
Other Names:
  • Imbruvica
Experimental: Arm A: IV Infusion of Ziloveramab and Oral Ibrutinib
Randomized, Double-Blind Treatment Phase
Drug: Ibrutinib
All participants will receive oral Ibrutinib (560mg) daily.
Other Names:
  • Imbruvica
Drug: Zilovertamab
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.
Other Names:
  • Cirmtuzumab
  • UC961
Placebo Comparator: Arm B: IV Infusion of Placebo and Oral Ibrutinib
Randomized, Double-Blind Treatment Phase
Drug: Ibrutinib
All participants will receive oral Ibrutinib (560mg) daily.
Other Names:
  • Imbruvica
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Approximately 2 years
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.
Approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Approximately 4 years
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.
Approximately 4 years
Duration of Response (DOR)
Time Frame: Approximately 4 years
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.
Approximately 4 years
Complete Response Rate
Time Frame: Approximately 4 years
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.
Approximately 4 years
Proportion of subjects experiencing Grade 3 to 4 neutrophil count decrease
Time Frame: Approximately 4 years
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.
Approximately 4 years
Overall Survival (OS)
Time Frame: Approximately 4 years
OS among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo.
Approximately 4 years
Overall Safety Profile
Time Frame: Approximately 4 years
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.
Approximately 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oncternal Therapeutics, Inc

Collaborators

Pharmacyclics LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2023

Primary Completion (Anticipated)

November 1, 2026

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

June 9, 2022

First Submitted That Met QC Criteria

June 21, 2022

First Posted (Actual)

June 24, 2022

Study Record Updates

Last Update Posted (Actual)

April 21, 2023

Last Update Submitted That Met QC Criteria

April 19, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZILO-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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