Phase 2
N=507
A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies
Chronic Myelogenous Leukemia · Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) · Hypereosinophilic Syndrome · Systemic Mastocytosis
Bottom Line
View on ClinicalTrials.gov: NCT00109707 ↗Enrolled (actual)
507
Serious AEs
43.8%
Results posted
Jun 2021
Primary outcome: Primary: Number of Participants With Major Cytogenetic Response (MCyR) — 191; 44; 22 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Nilotinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Sep 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Major Cytogenetic Response (MCyR) |
191; 44; 22 | — |
| PRIMARY Number of Participants Confirmed Overall Hematological Response (Phase II) |
76 | — |
| SECONDARY Number of Participants With Overall Major Cytogenetic Responses (Phase II) |
191; 44; 22 | — |
| SECONDARY Number of Participants With Complete Hematologic Response (Phase II) |
158; 76; 27 | — |
| SECONDARY Participants With (MMR) Major Molecular Response (Phase II) |
106; 18 | — |
| SECONDARY Time to Progression (TTP) (Phase II) |
55.6; 15.9 | — |
| SECONDARY Overall Survival (OS) (Phase II) |
NA; 47.54; NA | — |
| SECONDARY Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety |
61; 26; 5; 57; 17; 7 | — |
Summary
The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions:
Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1)
Group A - Imatinib failure only (arms 2, 3 and 4)
* imatinib-resistant or intolerant CML - Chronic Phase (CP)
* imatinib-resistant or intolerant CML - Accelerated Phase (AP)
* imatinib-resistant or intolerant CML - Blast Crisis (BC)
Group B - Imatinib and other TKI failure (arms 2, 3 and 4)
* imatinib-resistant or intolerant CML - Chronic Phase (CP)
* imatinib-resistant or intolerant CML - Accelerated Phase (AP)
* imatinib-resistant or intolerant CML - Blast Crisis (BC)
Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5)
Systemic mastocytosis (Sm) (arm 6)
Eligibility Criteria
Inclusion Criteria
Main inclusion criteria include:
- Patients with CML in blast crisis, CML in accelerated phase defined as never in blast crisis phase, or CML in chronic phase defined as never been in blast crisis phase or accelerated phase who have: *developed progressive disease during therapy with at least 600 mg of imatinib per day, -OR- *patients with CML on imatinib therapy, at any dose, developing progressive disease and the presence of a genetic mutation likely to result in imatinib resistance -OR- *have developed an intolerance to imatinib
- Relapsed or refractory Ph+ ALL
- Hypereosinophilic syndrome/chronic eosinophilic leukemia.
- Systemic mastocytosis who have a clinical indication for treatment.
- Prior imatinib therapy for patients with Ph+ ALL, HES/CEL and SM is permitted but is not required
- CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition of imatinib-resistance or intolerance are eligible
- Written informed consent prior to any study procedures being performed
Exclusion Criteria
- Impaired cardiac function
- Patients with severe/chronic or uncontrolled medical conditions (including but not limited to diabetes, infections, GI impairment, CNS infiltration, liver and kidney disease)
- Prior and concomitant use of certain medications (including but not limited to warfarin, chemotherapy, hematopoietic colony-stimulating growth factors, medications that can affect electrocardiogram test results, other investigational drugs )
- Women who are pregnant or breastfeeding
- Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
- Patients unwilling to comply with the protocol.
- Known diagnosis of human immunodeficiency virus (HIV) infection
Other protocol-defined inclusion/exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT00109707). 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.