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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05431179
• Other study ID #: ZILO-301
• Status: Withdrawn
• Phase: Phase 3
• Start date: March 2023
• Est. completion date: December 2026

Study information

• Verified date: April 2023
• Source: Oncternal Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2026
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Immune System Diseases
• Immunoproliferative Disorders
• Lymphatic Diseases
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoproliferative Disorders

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Oncternal Therapeutics, Inc	Pharmacyclics LLC.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Approximately 2 years
Secondary	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.	Approximately 4 years
Secondary	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.	Approximately 4 years
Secondary	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.	Approximately 4 years
Secondary	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.	Approximately 4 years
Secondary	Overall Survival (OS)	OS among the subjects who received the combination of zilovertamab plus ibrutinib compared with the subjects who received ibrutinib plus placebo.	Approximately 4 years
Secondary	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.	Approximately 4 years