NCT03884972

Trabectedin and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Resistant or Intolerant to a BTK Inhibitor

A Phase I/Ib Pilot Study of Combined Trabectedin and Venetoclax in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Resistant or Intolerant to a BTK Inhibitor

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/Ib trial studies the best dose and side effects of trabectedin and venetoclax in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that is resistant or intolerant to a BTK inhibitor. Drugs used in chemotherapy, such as trabectedin and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate safety and tolerability, and to determine dose and schedule of trabectedin in combination with venetoclax in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) resistant or intolerant to a BTK inhibitor. SECONDARY OBJECTIVES: I. To determine the best response achieved by patients treated with combined trabectedin and venetoclax. II. To determine the progression-free (PFS) and overall survival (OS) of patients treated with combined trabectedin and venetoclax. III. To investigate the effects of trabectedin on CLL cells and on the components of the CLL microenvironment. IV. To investigate associations between baseline characteristics (including fluorescence in situ hybridization \[FISH\] status, IGHV mutation status and mutations responsible for resistance to BTK inhibitors) and response to the combination of trabectedin and venetoclax. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts. COHORT I (BTK-REFRACTORY): Patients receive venetoclax orally (PO) once daily (QD) beginning on day 1 for 5 weeks (cycle 1). Beginning in cycle 2, patients receive venetoclax PO QD and trabectedin intravenously (IV) over 3 hours on day 1. Cycles 2+ repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. COHORT II (BTK-INTOLERANT): Patients receive trabectedin IV over 3 hours on day 1 of a 3-week cycle (cycle 1), then receive venetoclax PO QD beginning on day 1 of a 5-week cycle (cycle 2). Beginning in cycle 3, patients receive trabectedin IV over 3 hours on day 1 and venetoclax PO QD every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.

Conditions

• Refractory Chronic Lymphocytic Leukemia
• Refractory Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	Trabectedin	Given IV
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2019-06-18
• Primary completion: 2020-03-04
• Completion: 2020-03-04
• First posted: 2019-03-21
• Last updated: 2023-09-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study