A Phase I-II Study to Determine the Safety, Pharmacokinetics and Potential Efficacy of Intravenous Administration of SB-743921 on Days 1 and 15 of a 28-Day Dosing Schedule in Patients With Non-Hodgkin Lymphoma and Hodgkin Lymphoma

Cytokinetics8 sites in 2 countries68 target enrollmentApril 2006

ConditionsNon-Hodgkin's Lymphoma Hodgkin's Disease

InterventionsSB-743921

DrugsSB-743921

Overview

Phase: Phase 1
Intervention: SB-743921
Conditions: Non-Hodgkin's Lymphoma
Sponsor: Cytokinetics
Enrollment: 68
Locations: 8
Primary Endpoint: Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF.
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study was an early-phase trial arranged into two phases. The Phase I portion was a dose-escalation study designed to assess the safety, tolerability and to identify the maximum tolerated dose of SB-743921 in patients with Non-Hodgkin Lymphoma and Hodgkin Lymphoma. Phase II was intended to assess the activity, safety and tolerability of SB-743921 in patients with Indolent and Aggressive Non-Hodgkin's Lymphomas exclusively. The Phase II portion of the study was not initiated.

Registry

clinicaltrials.gov

Start Date

April 2006

End Date

July 2010

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Cytokinetics

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Phase 1: Patients with evaluable or measurable (by MRI or CT) Hodgkin's Disease or Non-Hodgkin's Lymphoma. Phase 2: Patients with Measurable Non-Hodgkin's Lymphomas (Indolent or Aggressive) only. - Patients with Indolent NHL must be relapsed or refractory to at least one prior line of therapy (CHOP, CVP, chlorambucil or fludaribine). Prior treatment with Rituximab is required. - Patients with Aggressive NHL refractory to (or relapsed from) at least one CHOP-based therapy who have had prior treatment with Rituximab and who are not candidates for high-dose chemotherapy or autologous stem cell transplantation. - ECOG performance status 0-2 - Autologous stem cell transplant recipients are eligible if 100 days have elapsed since procedure.

Exclusion Criteria

•Phase 1: History of prior radioimmunotherapy (Bexxar, Zevalin); These patients ARE permitted in the Phase 2 trial. - Current active malignancy besides NHL, except excised non-melanoma skin cancer, in-situ cervical or bladder cancer or early stage prostate cancer. - Patients with leptomeningeal of CNS lymphoma - Known allergy to and/or receipt of treatments contraindicated by administration of G-CSF - Patients with active Hepatitis B or C, or patients with HIV infection. - Pregnant or breast-feeding females. - Previous treatment with a KSP inhibitor

Arms & Interventions

Phase 1 Dose Escalation

Phase 1 dose escalation without and with GCSF support

Intervention: SB-743921

Phase 2 Fixed Dose

Phase 2 fixed dose based on Phase I findings stratified by NHL type

Intervention: SB-743921

Outcomes

Primary Outcomes

Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF.

Time Frame: 28 days

Maximum Tolerated Dose (MTD) was determined by testing increasing doses in cohorts with at least 3 patients each. MTD reflects the highest dose of drug that did not cause dose limiting toxicity (DLT).

Secondary Outcomes

Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)
Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)
Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)
Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)
Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)
Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)
Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)
Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15(Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose)