Clinical trial NCT00343564: A Study of SB-743921 in Non-Hodgkin Lymphoma and Hodgkin Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Hodgkin's Disease
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2006-06-23
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF.
timeFrame: 28 days
Secondary outcomes:
measure: Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
measure: Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
measure: Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
measure: Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
measure: Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
measure: Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
measure: Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
measure: Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
timeFrame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Cornell University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Caner Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Cancer Research Institute
state: Tennessee
city: Moscow
country: Russian Federation
facility: Russian Medical Academy of Postgraduate Education
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State PAVLOV Medical University
Study officials:
affiliation: Columbia University
name: Owen O'Connor, M.D./Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: O'Connor OA, Gerecitano J, Van Deventer H, Hainsworth J, Zullo KM, Saikali K, Seroogy J, Wolff A, Escandon R. The addition of granulocyte-colony stimulating factor shifts the dose limiting toxicity and markedly increases the maximum tolerated dose and activity of the kinesin spindle protein inhibitor SB-743921 in patients with relapsed or refractory lymphoma: results of an international, multicenter phase I/II study. Leuk Lymphoma. 2015;56(9):2585-91. doi: 10.3109/10428194.2015.1004167. Epub 2015 Sep 11.