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

NCT05431179 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: ZILO-301
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

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

Keywords

Mantle cell lymphoma; Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1); Bruton Tyrosine Kinase (BTK) inhibitor; Ibrutinib; Zilovertamab

Outcome Measures

Primary Outcomes (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.

  Approximately 2 years

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Approximately 4 years

• Duration of Response (DOR)

  Approximately 4 years

• Complete Response Rate

  Approximately 4 years

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

  Approximately 4 years

• Overall Survival (OS)

  Approximately 4 years

Study Arms (3)

Oral Ibrutinib

EXPERIMENTAL

Open Label Ibrutinib Monotherapy Phase (16 weeks)

Drug: Ibrutinib

Arm A: IV Infusion of Ziloveramab and Oral Ibrutinib

EXPERIMENTAL

Randomized, Double-Blind Treatment Phase

Drug: Zilovertamab; Drug: Ibrutinib

Arm B: IV Infusion of Placebo and Oral Ibrutinib

PLACEBO COMPARATOR

Randomized, Double-Blind Treatment Phase

Drug: Ibrutinib; Drug: Placebo

Interventions

Zilovertamab 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.

Also known as: Cirmtuzumab, UC961

Arm A: IV Infusion of Ziloveramab and Oral Ibrutinib

Ibrutinib DRUG

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

Also known as: Imbruvica

Arm A: IV Infusion of Ziloveramab and Oral Ibrutinib; Arm B: IV Infusion of Placebo and Oral Ibrutinib; Oral Ibrutinib

Placebo 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.

Arm B: IV Infusion of Placebo and Oral Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oncternal Therapeutics, Inc: lead
• Pharmacyclics LLC.: collaborator

Related 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.

  PMID: 25113753 BACKGROUND

MeSH Terms

Conditions

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

Interventions

cirmtuzumab; ibrutinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 24, 2022
• Study Start: March 1, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 21, 2023

Record last verified: 2023-04