Phase 3
N=846
A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Myelogenous Leukemia, Chronic
Bottom Line
View on ClinicalTrials.gov: NCT00471497 ↗Enrolled (actual)
846
Serious AEs
40.0%
Results posted
Jun 2013
Primary outcome: Primary: Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation — 22.3; 44.3; 42.7 Percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- nilotinib (Drug); imatinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Sep 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation |
22.3; 44.3; 42.7 | <0.0001 sig |
| PRIMARY Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation |
26.0; 40.8; 53.4; 22.8; 50.5; 40.0 | — |
| SECONDARY Rates of Durable MMR at 24 Months Between All 3 Arms |
20.5; 41.8; 39.1 | — |
| SECONDARY Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months |
55.5; 70.2; 68.7; 61.5; 66.0; 66.2 | — |
| SECONDARY Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms |
44.3; 42.7 | 0.6987 |
| SECONDARY Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms |
12.0; 33.0; 29.5; 22.3; 44.7; 43.1 | — |
| SECONDARY Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib |
1.1; 8.9; 5.7; 3.9; 12.1; 8.9 | — |
| SECONDARY Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib |
0.0; 3.5; 1.4; 0.4; 4.6; 5.0 | — |
| SECONDARY Time to First MMR |
14.13; 8.31; 8.53 | — |
| SECONDARY Duration of MMR |
NA; NA; NA | — |
| SECONDARY Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts |
30.46; 19.38; 22.70; 37.29; 32.46; 35.94 | — |
| SECONDARY Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Rate of Hematologic Response |
93.3; 90.1; 89.0; 93.6; 90.8; 90.4 | — |
| SECONDARY Time to Complete Cytogenic Response (CCyR) |
8.5; 5.7; 5.7 | — |
| SECONDARY Duration of CCyR |
NA; NA; NA | — |
| SECONDARY Progression-free Survival (PFS) |
NA; NA; NA | — |
| SECONDARY Event-free Survival (EFS) |
NA; NA; NA | — |
| SECONDARY Overall Survival (OS) |
NA; NA; NA | — |
| SECONDARY Actual Dose-intensity |
400.0; 591.1; 758.9 | — |
| SECONDARY Time to Progression to AP/BC |
NA; NA; NA | — |
| SECONDARY Pharmacokinetics: Cmax |
1555; 1440 | — |
| SECONDARY Pharmacokinetics: Cmin |
1430; 915 | — |
| SECONDARY Pharmacokinetics: Tmax |
1.47; 1.50 | — |
| SECONDARY Pharmacokinetics: AUC0-last |
14446; 11689 | — |
| SECONDARY Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) |
83.3; 84.6; 66.7 | — |
| SECONDARY Rate of Complete Cytogenetic Response (CCyR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) |
72.9; 73.1; 66.7 | — |
| SECONDARY Rate of Major Molecular Response (MMR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) |
64.6; 73.1; 66.7 | — |
| SECONDARY Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) |
43.8; 57.7; 33.3 | — |
| SECONDARY Rate of ≥ 4.5 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) |
35.4; 38.5; 33.3 | — |
| SECONDARY Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension) |
20.8; 11.5; 33.3 | — |
Summary
In this study, the efficacy and safety of two nilotinib doses, 300 mg twice daily and 400 mg twice daily, were compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).
An extension protocol was included in this study design to allow patients who did not show sufficient response to their assigned treatments the opportunity to receive imatinib 400 mg BID (option available until protocol amendment 7) or nilotinib 400 mg BID, using an abbreviated safety and efficacy assessment schedule.
Eligibility Criteria
Key Inclusion criteria
- Chronic myelogenous leukemia in chronic phase patients within the first 6 months of diagnosis.
- Diagnosis of chronic myelogenous leukemia in chronic phase with confirmation of Philadelphia chromosome of (9:22) translocations
Key Exclusion criteria
- Previously documented T315I mutation
- Treatment with a tyrosine kinase inhibitor prior to study entry is not allowed except for no more than 2 weeks in duration of imatinib
- Any medical treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide
- Impaired cardiac function.
- Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
- Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
- Currently receiving treatment with any medications that have the potential to prolong the QT interval.
Data sourced from ClinicalTrials.gov (NCT00471497). 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.