NCT03454165

A Study of BNC105P Combined With Ibrutinib

A Phase 1 Trial of BNC105P & Ibrutinib in Patients w/ Relapsed/Refractory CLL

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Dartmouth-Hitchcock Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia(CLL). This study proposes that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. The study will establish the maximum tolerated dose(MTD) of the combination of BNC105P with ibrutinib, characterize the pharmacodynamic effects of BNC105P alone and in combination with ibrutinib in CLL cells, and provide preliminary assessment of the efficacy of the combination in CLL. The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued

Detailed description

A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Ibrutinib inhibits the pro-survival BCR signaling of CLL cells in the stromal niche resulting in their egress to the periphery. Importantly, if administration of ibrutinib is stopped, the CLL cells rapidly return to the lymph node. In some patients, the drug-induced increase in circulating CLL cells has been seen for more than a year reflecting the fact that the cells do not readily die once they exit the lymph node. Resistance to ibrutinib has been observed as mutations in the drug-binding cysteine in its target, BTK. This resistance is likely to become far more prevalent as patients remain on ibrutinib for months or years. We propose that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. BNC105P works through an entirely different mechanism, i.e. tipping the balance of pro-survival and pro-apoptotic BCL2 family member proteins toward the latter, resulting in cell death. This pathway of apoptosis occurs at all stages of the cell cycle which is important considering that the majority of peripheral CLL cells are non-cycling (in G0). The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued.

Conditions

• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
COMBINATION_PRODUCT	BNC105P	BNC105P is the phosphate ester of BNC105, a small molecule tubulin polymerization inhibitor.
COMBINATION_PRODUCT	Ibrutinib	A novel BTK inhibitor.

Timeline

• Start date: 2018-03-09
• Primary completion: 2021-01-14
• Completion: 2021-01-14
• First posted: 2018-03-05
• Last updated: 2023-01-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study