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

NCT ID: NCT05431179

Last Updated: 2023-04-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-31
• Study Completion Date: 2026-12-31

Brief 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).

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oral Ibrutinib

Open Label Ibrutinib Monotherapy Phase (16 weeks)

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

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

Arm A: IV Infusion of Ziloveramab and Oral Ibrutinib

Randomized, Double-Blind Treatment Phase

Group Type: EXPERIMENTAL

Zilovertamab

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Arm B: IV Infusion of Placebo and Oral Ibrutinib

Randomized, Double-Blind Treatment Phase

Group Type: PLACEBO_COMPARATOR

Ibrutinib

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Ibrutinib

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Cirmtuzumab; UC961; Imbruvica

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: collaborator

Oncternal Therapeutics, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: BACKGROUND

PMID: 25113753 (View on PubMed)

Other Identifiers

ZILO-301

Identifier Type: -

Identifier Source: org_study_id