NCT00676871

A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of Continuous Intravenous Infusion of MEDI-538 in Adults With B-Cell Chronic Lymphocytic Leukemia (CLL)

A Phase 1/2, Open-Label, Single-Arm, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of Continuous Intravenous Infusion of the Bispecific T-Cell Engager MEDI-538 In Adults With B-Cell Chronic Lymphocytic Leukemia(CLL)Who Have Residual Disease Following Previous Therapy for CLL

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: MedImmune LLC · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Phase 1: * Evaluate the safety and tolerability of MEDI-538 given by escalated doses with continuous IV infusion for 4 weeks in adult patients with CLL. * Determine the maximum tolerated dose (MTD) of MEDI-538 administered by continuous IV infusion for 4 weeks in this patient population * Describe the pharmacokinetics (PK) of MEDI-538 * Describe the immunogenicity (IM) of MEDI-538 * Determine the overall response, which is defined as follows: (1) conversion from PD/SD to PR/nPR/CR or conversion from PR to nPR/CR using standard NCI-WG criteria; or (2) conversion from MRD positivity to MRD negativity using 4-color flow cytometry; and * Describe any antitumor activity (ie, time to response and duration of response) of MEDI-538 in this patient population. Phase 2: * To determine the overall response in adult patients with CLL who have residual disease following previous therapy for CLL. * Describe the safety,PK,and IM of MEDI-538 * Determine the time to MRD relapse * Determine the antitumor activity (ie, time to response, duration of response,and time to progression \[TTP\])of MEDI-538 in this patient population.

Detailed description

Phase 1: * Evaluate the safety and tolerability of MEDI-538 at doses of 5, 10, 15, 30, 45, or 60 mg/m2/24h by continuous IV infusion for 4 weeks in adult patients with CLL who have measurable disease following previous therapy for CLL. Patients with measurable disease include patients who demonstrated PD, SD, or PR following previous therapy for CLL; and * Determine the maximum tolerated dose (MTD) of MEDI-538 administered by continuous IV infusion for 4 weeks in this patient population; * Describe the pharmacokinetics (PK) of MEDI-538 * Describe the immunogenicity (IM) of MEDI-538 * Determine the overall response, which is defined as follows: (1) conversion from PD/SD to PR/nPR/CR or conversion from PR to nPR/CR using standard NCI-WG criteria; or (2) conversion from MRD positivity to MRD negativity using 4-color flow cytometry; and * Describe any antitumor activity (ie, time to response and duration of response) of MEDI-538 in this patient population. Phase 2: * Determine the overall response in adult patients with CLL who have residual disease following previous therapy for CLL. * Describe the safety of MEDI-538 * Describe the PK of MEDI-538 * Describe the IM of MEDI-538 * Determine the time to MRD relapse * Determine the antitumor activity (ie, time to response, duration of response, and time to progression \[TTP\]) of MEDI-538 in this patient population.

Conditions

• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	MEDI-538	Dose one of MEDI 538 as a continuous IV infusion - dose level is 5 mg/m2/24h (Phase 1)
DRUG	MEDI-538	Dose two of MEDI 538 as a continuous IV infusion - dose level is 10 mg/m2/24h (Phase 1)
DRUG	MEDI-538	Dose three of MEDI 538 as a continuous IV infusion-dose level is 15mg/m2/24h (Phase 1)
DRUG	MEDI-538	Dose four of MEDI 538 as a continuous IV infusion - dose level is 30 mg/m2/24h(Phase 1)
DRUG	MEDI-538	Dose five of MEDI 538 as a continuous IV infusion - dose level is 45 mg/m2/24h (Phase 1)
DRUG	MEDI-538	Dose six of MEDI 538 as a continuous IV infusion - dose level is 60 mg/m2/24h (Phase 1)
DRUG	MEDI-538	Phase 2 part of the study, 20 to 60 patients will be treated with MEDI 538 as a continuous IV infusion through a central line catheter. The dose of MEDI-538 will be determined in the Phase 1 part of the study.

Timeline

• Start date: 2008-06-01
• Primary completion: 2010-03-01
• Completion: 2011-06-01
• First posted: 2008-05-13
• Last updated: 2008-09-05