Phase 2
N=18
Study Evaluating SKI-606 (Bosutinib) In Philadelphia Chromosome Positive Leukemias
Chronic Myeloid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT00261846 ↗Enrolled (actual)
18
Serious AEs
44.2%
Results posted
Mar 2013
Primary outcome: Primary: Number of Participants With Dose Limiting Toxicity (DLT) — 0; 0; 1 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bosutinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Sep 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicity (DLT) |
0; 0; 1 | — |
| PRIMARY Maximum Tolerated Dose (MTD) |
NA; NA; NA | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) - Part 1 |
89.3; 101.0; 120.0 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1 |
4.00; 6.00; 4.00 | — |
| PRIMARY Plasma Decay Half-Life (t1/2) - Part 1 |
22.91; 22.46; 22.24 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC(0-48)] - Part 1 |
1850; 2060; 2340 | — |
| PRIMARY Area Under the Concentration-Time Curve (AUC) - Part 1 |
2530; 2760; 2420 | — |
| PRIMARY Apparent Oral Clearance (CL/F) - Part 1 |
177; 189; 258 | — |
| PRIMARY Apparent Volume of Distribution (Vz/F) - Part 1 |
6050; 6080; 8540 | — |
| PRIMARY Maximum Observed Plasma Concentration at Steady State (Cmax,ss) - Part 1 |
146; 200; 208 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) - Part 1 |
4.05; 6.05; 6.00 | — |
| PRIMARY Plasma Decay Half-Life at Steady State (t1/2,ss) - Part 1 |
45.96; 21.71; 25.87 | — |
| PRIMARY Area Under the Concentration-Time Curve at Steady State (AUCss) - Part 1 |
2720; 3650; 3630 | — |
| PRIMARY Apparent Oral Clearance at Steady State (CL/F,ss) - Part 1 |
150; 138; 185 | — |
| PRIMARY Accumulation Ratio (R) |
3.1; 2.8; 2.5 | — |
| PRIMARY Percentage of Participants With MCyR at Week 24 in Chronic Phase Second-line Imatinib Resistant CML Population - Part 2 |
35.7 | — |
| SECONDARY Percentage of Participants With Major Cytogenetic Response (MCyR) - Part 1 |
66.7; 33.3; 50.0 | — |
| SECONDARY Phosphorylation Inhibition of Breakpoint Cluster Region-Abelson Kinase (Bcr-Abl) - Part 1 |
— | — |
| SECONDARY Phosphorylation Inhibition of Crk Like (CrkL) Protein at Baseline - Part 1 |
457075; 297967.33; 397795.40 | — |
| SECONDARY Percent Change From Baseline in Phosphorylation Inhibition of Crk Like Protein (CrkL) at Day 1, 8 and 15 - Part 1 |
-34.66; 287.52; 97.79; 562.48; 170.83; 3.88 | — |
| SECONDARY Percentage of Participants With Major Cytogenetic Response (MCyR) in Chronic Phase Second-line and Chronic Phase Third-line CML Population - Part 2 |
61.3; 40.0; 38.9; 42.2; 38.5; 58.8 | — |
| SECONDARY Kaplan-Meier Estimate of Retaining an Attained/Maintained Major Cytogenetic Response (MCyR) at Year 5 in Chronic Phase Second-line CML - Part 2 |
67.2; 79.8 | — |
| SECONDARY Time to Achieve Major Cytogenetic Response (MCyR) in Chronic Phase Second-line CML for Responders Only - Part 2 |
12.3; 12.1 | — |
| SECONDARY Kaplan-Meier Estimate of Maintaining Complete Hematologic Response (CHR) at Year 4 (CP3L and ADV) or Year 5 (CP2L) - Part 2 |
61.5; 78.2; 50.0; 56.5; 69.9; 61.9 | — |
| SECONDARY Duration of Complete Hematologic Response (CHR) - Part 2 |
NA; 350.4; NA; NA; 295.6; NA | — |
| SECONDARY Time to Achieve Complete Hematologic Response (CHR) for Responders Only - Part 2 |
2.0; 1.3; 1.6; 1.2; 1.3; 2.4 | — |
| SECONDARY Cumulative Incidence of Progression/Death - Part 2 |
10.8; 4.5; 20.0; 23.7; 12.0; 23.1 | — |
| SECONDARY Progression Free Survival (PFS) - Part 2 |
NA; 81.5; NA; NA; NA; NA | — |
| SECONDARY Kaplan-Meier Estimate of Overall Survival (OS) - Part 2 |
96.3; 98.9; 100; 85.8; 91.8; 96.2 | — |
| SECONDARY Overall Survival (OS) - Part 2 |
NA; 81.5; NA; NA; NA; NA | — |
| SECONDARY Percentage of Participants With Confirmed Complete Hematologic Response (CHR) - Part 2 |
87.1; 85.4; 80.0; 68.4; 75.5; 76.0 | — |
| SECONDARY Percentage of Participants With Overall Hematologic Response (OHR) by Week 48 in Advanced Leukemia Population - Part 2 |
67.4; 41.4; 38.2; 15.4; 9.1 | — |
| SECONDARY Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) |
99.5; 100.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY Duration of Potentially Clinically Important (PCI) Adverse Events (AEs) |
14.0; 36.0; 38.0; 19.0; 13.0; 61.0 | — |
| SECONDARY Percentage of Participants With Change From Baseline in Laboratory Tests Results |
0.5; 1.1; 0.0; 0.0; 0.0; 3.8 | — |
| SECONDARY Percentage of Participants With On-treatment PCI Change From Baseline in Electrocardiogram (ECG) Findings |
32.3; 23.6; 20.0; 24.3; 22.0; 23.1 | — |
| SECONDARY Number of Participants With Change From Baseline in Findings of Chest X-ray |
35; 18; 1; 6; 18; 3 | — |
| SECONDARY Number of Participants Who Received Concomitant Medications for Management of Adverse Events (AEs) |
7; 3; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS) |
92; 36; 2; 21; 20; 19 | — |
| SECONDARY Percentage of Participants With Change From Baseline in Physical Examinations and Vital Signs |
1.1; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Change From Baseline in Physical Examinations and Vital Signs and Number of Participants With PCI Values |
4.2; 0; 0; 0; 0; 0 | — |
Summary
This is an open-label, continuous daily dosing, two-part safety and efficacy study of SKI-606 (bosutinib) in Philadelphia chromosome positive leukemias (Ph+). Part 1 is a dose-escalation study in chronic phase Chronic Myelogenous Leukemia (CML) subjects to establish the maximum tolerated dose (MTD) in this subject population. Part 2 has begun after the completion of Part 1 and after a dose has been established for the compound in chronic phase subjects. Part 2 is a study of the the efficacy of 500mg daily oral SKI-606 (bosutinib) in patients with all phases of Ph+ CML and Ph+ Acute Lymphocytic Leukemia (ALL). The protocol will test the hypotheses that oral daily dosing of bosutinib at 500 mg will attain (1) Major Cytogenetic Response (MCyR) in chronic phase CML patients and (2) Overall Hematological Response (OHR) in advanced leukemia patients. Each phase of the disease will be evaluated as a separate cohort.
Eligibility Criteria
Inclusion Criteria
- Ph+ CML or Ph+ ALL who are primarily refractory to full-dose imatinib (600 mg), have disease progression/relapse while on full-dose imatinib, or are intolerant of any dose of imatinib.
- At least 3 months post stem cell transplantation
- Able to take daily oral capsules/tablets reliably
Exclusion Criteria
- Subjects with Philadelphia chromosome, and bcr-abl negative CML
- Overt leptomeningeal leukemia
- Subjects without evidence of leukemia in bone marrow (extramedullary disease only)
Data sourced from ClinicalTrials.gov (NCT00261846). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.