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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-Hodgkin's Lymphoma, Hodgkin's Disease

Intervention / Treatment
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* Drug: SB-743921
* Drug: SB-743921


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Dose Escalation<br>Phase 1 dose escalation without and with GCSF support | Drug: SB-743921<br>* 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.<br>|
| Experimental: Phase 2 Fixed Dose<br>Phase 2 fixed dose based on Phase I findings stratified by NHL type | Drug: SB-743921<br>* Phase 2: I.V. dose and regimen will be determined based on Phase 1 findings.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 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). | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |