NCT03088878

A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies

A Phase 1b/2 Study of the ROR1-Targeting Monoclonal Antibody, Cirmtuzumab (UC-961), and the Bruton Tyrosine Kinase Inhibitor, Ibrutinib, in Patients With B-Cell Lymphoid Malignancies

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 95 (actual)
• Sponsor: Oncternal Therapeutics, Inc · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is Phase 1b/2 study to investigate the safety and effectiveness of the investigational drug, cirmtuzumab, when given in combination with ibrutinib in patients with B-cell lymphoid malignancies. Cirmtuzumab is a monoclonal antibody that attaches to a protein (called ROR 1) that is found on hematologic tumor cells. ROR1 has been shown to play a role in cell signaling that cause leukemia and lymphoma cells to grow and survive. ROR1 is rarely found on healthy cells.

Detailed description

This is a Phase 1b/2 study to investigate the safety and effectiveness of the investigational drug, cirmtuzumab (INN:zilovertamab), when given in combination with ibrutinib in patients with B-cell lymphoid malignancies. The Phase 1b will be conducted in two parts (Part 1 and Part 2). Part 1 is a dose-finding evaluation of the sequential administration of cirmtuzumab monotherapy followed by cirmtuzumab and ibrutinib combination therapy in chronic lymphocytic leukemia /small lymphocytic leukemia (CLL/SLL), previously treated mantle cell lymphoma (MCL) subjects that are BTKI naiive or have received a prior Bruton tyrosine kinase (BTK) inhibitor therapy, unless they demonstrated primary or acquired resistance to BTKi. Up to 48 subjects will be enrolled in Part 1 to determine the recommended dosing regimen (RDR). In Part 2, up to 60 subjects (CLL/SLL, MCL and MZL (marginal zone lymphoma) will be enrolled to further evaluate the safety and pharmacology of the cirmtuzumab and ibrutinib combination given at the RDR determined in Part 1 of the study. MZL subjects that have been previously treated and have relapsed after or progressed during at least one prior anti-CD20 -based therapy will be evaluated. In the Phase 2 (Part 3) portion of the study, approximately 30 subjects with CLL/SLL who may have received minimal prior BTK inhibitor therapy will be randomized to either Arm 1 (cirmtuzumab and ibrutinib) at the RDR or Arm 2 (ibrutinib alone) to evaluate the clinical activity and safety of the two arms.

Conditions

• B-cell Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma

Interventions

Type	Name	Description
DRUG	Cirmtuzumab (2-16 kg/mg) plus Ibrutinib	Participants will receive escalating doses of cirmtuzumab (2-16 mg/kg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 or 560 mg) orally once daily, starting at week 4.
DRUG	Cirmtuzumab (300mg) plus Ibrutinib	Participants will receive cirmtuzumab (300 mg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily.
DRUG	Cirmtuzumab (600 mg) plus ibrutinib	Participants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily.
DRUG	Cirmtuzumab (RDR) plus ibrutinib	Participants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter, plus ibrutinib (420 or 560 mg) orally once daily
DRUG	Cirmtuzumab plus ibrutinib	Arm A: Participants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily.
DRUG	Ibrutinib alone	Arm B: Participants will receive ibrutinib (420 mg) orally once daily

Timeline

• Start date: 2018-01-03
• Primary completion: 2024-09-25
• Completion: 2024-09-25
• First posted: 2017-03-23
• Last updated: 2025-02-12
• Results posted: 2025-02-12

Locations

12 sites across 1 country: United States

Regulatory

• FDA-regulated drug study