A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Systemic Mastocytosis; Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive); Chronic Myelogenous Leukemia; Hypereosinophilic Syndrome

Treatments: Drug: Nilotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00109707

CAMN107A2101

Details and patient eligibility

About

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)

Enrollment: 507 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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507 participants in 3 patient groups

CML-CP With Prior Imatinib Only

Experimental group

Description:

Imatinib-resistant / intolerant PH+ CML-CP patients

Treatment:

Drug: Nilotinib

CML-AP With Prior Imatinib Onl

Experimental group

Description:

Imatinib-resistant / intolerant PH+ CML-AP patients

Treatment:

Drug: Nilotinib

CML-CP

Experimental group

Description:

Imatinib-resistant / intolerant PH+ CML-CP patients

Treatment:

Drug: Nilotinib