Hodgkin's Disease, Non-Hodgkin's Lymphoma
Conditions
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.
Interventions
DRUGSB-743921
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.
Sponsors
Cytokinetics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 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
| Measure | Time frame |
|---|---|
| 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 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 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 |
| 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 |
Countries
Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2 mg/m2 Without GCSF Phase 1 dose escalation cohort 1 without GCSF support | 6 |
| 3 mg/m2 Without GCSF Phase 1 dose escalation cohort 2 without GCSF support | 7 |
| 4 mg/m2 Without GCSF Phase 1 dose escalation cohort 3 without GCSF support | 3 |
| 5 mg/m2 Without GCSF Phase 1 dose escalation cohort 4 without GCSF support | 7 |
| 6 mg/m2 Without GCSF Phase 1 dose escalation cohort 5 without GCSF support | 10 |
| 7 mg/m2 Without GCSF Phase 1 dose escalation cohort 6 without GCSF support | 9 |
| 6 mg/m2 With GCSF Phase 1 dose escalation cohort 1 with GCSF support | 4 |
| 7 mg/m2 With GCSF Phase 1 dose escalation cohort 2 with GCSF support | 3 |
| 8 mg/m2 With GCSF Phase 1 dose escalation cohort 3 with GCSF support | 3 |
| 9 mg/m2 With GCSF Phase 1 dose escalation cohort 4 with GCSF support | 8 |
| 10 mg/m2 With GCSF Phase 1 dose escalation cohort 5 with GCSF support | 8 |
| Total | 68 |
Baseline characteristics
| Characteristic | 8 mg/m2 With GCSF | 9 mg/m2 With GCSF | 2 mg/m2 Without GCSF | 3 mg/m2 Without GCSF | 4 mg/m2 Without GCSF | 5 mg/m2 Without GCSF | 6 mg/m2 Without GCSF | 7 mg/m2 Without GCSF | 6 mg/m2 With GCSF | 7 mg/m2 With GCSF | 10 mg/m2 With GCSF | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 4 Participants | 4 Participants | 7 Participants | 3 Participants | 3 Participants | 8 Participants | 6 Participants | 1 Participants | 2 Participants | 4 Participants | 43 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 17 | 48 years STANDARD_DEVIATION 22 | 62 years STANDARD_DEVIATION 9 | 43 years STANDARD_DEVIATION 13 | 33 years STANDARD_DEVIATION 9 | 57 years STANDARD_DEVIATION 22 | 48 years STANDARD_DEVIATION 16 | 42 years STANDARD_DEVIATION 24 | 69 years STANDARD_DEVIATION 12 | 63 years STANDARD_DEVIATION 11 | 56 years STANDARD_DEVIATION 20 | 52 years STANDARD_DEVIATION 19 |
| Region of Enrollment Russian Federation | 1 participants | 0 participants | 0 participants | 3 participants | 2 participants | 2 participants | 3 participants | 3 participants | 0 participants | 0 participants | 1 participants | 15 participants |
| Region of Enrollment United States | 2 participants | 8 participants | 6 participants | 4 participants | 1 participants | 5 participants | 7 participants | 6 participants | 4 participants | 3 participants | 7 participants | 53 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants | 6 Participants | 1 Participants | 2 Participants | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 29 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants | 6 Participants | 5 Participants | 2 Participants | 2 Participants | 7 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 6 / 6 | 3 / 3 | 6 / 6 | 10 / 10 | 8 / 9 | 4 / 4 | 3 / 3 | 3 / 3 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 2 / 5 | 0 / 6 | 0 / 3 | 0 / 6 | 3 / 10 | 1 / 9 | 1 / 4 | 1 / 3 | 0 / 3 | 1 / 7 | 3 / 7 |
Outcome results
Primary
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).
Time frame: 28 days
Population: Safety population; all patients who received at least 1 dose of study drug were included in the intent-to-treat/safety populations. Efficacy evaluable; any patient who received both cycles of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 2 mg/m2 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 3 mg/m2 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 4 mg/m2 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 5 mg/m2 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 6 mg/m2 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 6 mg/m2 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 6 mg/m2 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 7 mg/m2 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 8 mg/m2 |
| Dose Escalation Cohort 4 9 mg/m2 (w/GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 9 mg/m2 |
| Dose Escalation Cohort 5 10 mg/m2 (w/GCSF) | Phase 1: Determination of Maximum Tolerated Dose (MTD) First Without and Then With Administration of Prophylactic G-CSF. | 9 mg/m2 |
Secondary
Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 1807 hr*ng/mL | Standard Deviation 1104 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 2800 hr*ng/mL | Standard Deviation 988.6 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 3269 hr*ng/mL | Standard Deviation 950.2 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 3707 hr*ng/mL | Standard Deviation 1750 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 5838 hr*ng/mL | Standard Deviation 2588 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 5359 hr*ng/mL | Standard Deviation 3028 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 6270 hr*ng/mL | Standard Deviation 2751 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 5875 hr*ng/mL | Standard Deviation 3483 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 11570 hr*ng/mL | Standard Deviation 6318 |
Secondary
Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1809 hr*ng/mL | Standard Deviation 464.1 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 2363 hr*ng/mL | Standard Deviation 1187 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 3380 hr*ng/mL | Standard Deviation 1456 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 4105 hr*ng/mL | Standard Deviation 2190 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 5869 hr*ng/mL | Standard Deviation 3417 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 5116 hr*ng/mL | Standard Deviation 1728 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 6041 hr*ng/mL | Standard Deviation 3010 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 6178 hr*ng/mL | Standard Deviation 3630 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (AUClast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 12590 hr*ng/mL | Standard Deviation 17850 |
Secondary
Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 36.9 ng/mL | Standard Deviation 23.6 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 61.6 ng/mL | Standard Deviation 29.4 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 59.5 ng/mL | Standard Deviation 39.9 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 79.1 ng/mL | Standard Deviation 51.9 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 133 ng/mL | Standard Deviation 64.7 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 103 ng/mL | Standard Deviation 48.3 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 144 ng/mL | Standard Deviation 97.6 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 122 ng/mL | Standard Deviation 69.6 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 245 ng/mL | Standard Deviation 134 |
Secondary
Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 29.2 ng/mL | Standard Deviation 11.8 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 84.2 ng/mL | Standard Deviation 60.8 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 58.5 ng/mL | Standard Deviation 29.8 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 84.6 ng/mL | Standard Deviation 47.9 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 138 ng/mL | Standard Deviation 103 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 92.4 ng/mL | Standard Deviation 50.5 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 138 ng/mL | Standard Deviation 94.9 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 150 ng/mL | Standard Deviation 105 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (Clast) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 285 ng/mL | Standard Deviation 290 |
Secondary
Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 172 ng/mL | Standard Deviation 40.7 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 348 ng/mL | Standard Deviation 86.6 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 357 ng/mL | Standard Deviation 50.4 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 514 ng/mL | Standard Deviation 177 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 600 ng/mL | Standard Deviation 175 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 689 ng/mL | Standard Deviation 401 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 1130 ng/mL | Standard Deviation 189 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 805 ng/mL | Standard Deviation 501 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 1 | 1180 ng/mL | Standard Deviation 682 |
Secondary
Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 220 ng/mL | Standard Deviation 51.2 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 323 ng/mL | Standard Deviation 120 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 365 ng/mL | Standard Deviation 45.2 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 599 ng/mL | Standard Deviation 383 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 717 ng/mL | Standard Deviation 278 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 835 ng/mL | Standard Deviation 442 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 685 ng/mL | Standard Deviation 163 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 706 ng/mL | Standard Deviation 344 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (Cmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1430 ng/mL | Standard Deviation 1620 |
Secondary
Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.20 hr | Standard Deviation 0.45 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.08 hr | Standard Deviation 0.28 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.00 hr | Standard Deviation 0.43 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day1 | 1.17 hr | Standard Deviation 0.41 |
Secondary
Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15
Time frame: Pre-dose, immediately post-dose, between 2 and 4 hours post-dose and between 24 and 36 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1 2 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 2 3 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 3 4 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 4 5 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 5 6 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 6 7 mg/m2 (w/o GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 1 6 mg/m2 (w/ GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 2 7mg/m2 (w/GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |
| Dose Escalation Cohort 3 8 mg/m2 (w/GCSF) | Characterization of PK (Tmax) of SB-743921 Administered as a 1-hour Intravenous Infusion on Day 15 | 1.00 hr | Standard Deviation 0 |