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

A Study of SB-743921 in Non-Hodgkin Lymphoma and Hodgkin Lymphoma

Sponsors

Lead sponsor: Cytokinetics

Source Cytokinetics
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.

Overall Status Completed
Start Date April 2006
Completion Date July 2010
Primary Completion Date July 2010
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. 28 days
Secondary Outcome
Measure Time Frame
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
Enrollment 68
Condition
Intervention

Intervention type: Drug

Intervention name: SB-743921

Description: Phase 1: I.V. dose on Days 1 and 15 of a 28 day cycle starting at 2mg/m2 and increasing by 1 mg/m2 with possible prophylactic granulopoietic support until unacceptable toxicity develops.

Arm group label: Phase 1 Dose Escalation

Intervention type: Drug

Intervention name: SB-743921

Description: Phase 2: I.V. dose and regimen will be determined based on Phase 1 findings.

Arm group label: Phase 2 Fixed Dose

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Owen O'Connor, M.D./Ph.D. Principal Investigator Columbia University
Location
facility
Hackensack University Medical Center | Hackensack, New Jersey, 07601, United States
Cornell University Medical Center | New York, New York, 10021, United States
Memorial Sloan-Kettering Caner Center | New York, New York, 10021, United States
Herbert Irving Comprehensive Cancer Center | New York, New York, 10032, United States
University of North Carolina | Chapel Hill, North Carolina, 27599, United States
Sarah Cannon Cancer Research Institute | Nashville, Tennessee, 37203, United States
Russian Medical Academy of Postgraduate Education | Moscow, 115478, Russian Federation
St. Petersburg State PAVLOV Medical University | Saint Petersburg, 197002, Russian Federation
Location Countries

Russian Federation

United States

Verification Date

January 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Phase 1 Dose Escalation

Arm group type: Experimental

Description: Phase 1 dose escalation without and with GCSF support

Arm group label: Phase 2 Fixed Dose

Arm group type: Experimental

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

Study Design Info

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov