Safety and Tolerability of Combined Treatment With Nilotinib and Ruxolitinib in CML and Ph+ ALL Patients

A Phase Ib Single-arm, Open-label, Multicenter Study to Assess the Safety and Tolerability of Combined Treatment With Nilotinib 300mg BID and Ruxolitinib Increasing Dose in CML and Ph+ ALL Patients

In this study it was the rationale to evaluate the safety and tolerability of the combined administration of nilotinib and increasing dose of ruxolitinib in patients with chronic myeloid leukemia and patients with Philadelphia positive acute lymphoblastic leukemia.

Inclusion Criteria:

Patients of the first stratum must have chronic myeloid leukemia receiving nilotinib first-line therapy or receiving second-line or subsequent-line treatment with nilotinib.

Patients of the second stratum must have CML in AP/BC or relapsed/refractory Ph+ ALL, or be Ph+ ALL patients with MRD with or without prior nilotinib pretreatment;

Patients must have adequate end organ function, as defined by:

• Creatinine < 2.0 x upper limit of normal (ULN)
• Total bilirubin < 1.5 x ULN (< 3.0 x ULN if related to disease or polymorphism, such as Mb. Gilbert)
• ALT and AST < 2.5 x ULN (< 5.0 x ULN if related to disease)
• Serum lipase ≤ 1.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN (< 5.0 x ULN if related to disease);

Patients must have the following electrolyte values within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication:

• Potassium
• Magnesium
• Phosphate
• Total calcium (corrected for serum albumin);

Female patients of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before initiation of study drug. All WOCBP must use highly effective contraceptive methods throughout and during 3 months after study;

Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 for patients in CP, ≤ 2 for patients in AP/BC or with relapsed/refractory Ph+ ALL or with Ph+ ALL with MRD;

Patient has the following laboratory values within 7 days of starting study drug:

- For CML and Ph+ ALL patients: platelet count > 75 x 109/L and ANC > 1.0 x 109/L

Exclusion Criteria:

Patient must not have evidence of active malignancy other than the existing CML or ALL

Patient must not receive drugs that interfere with coagulation or inhibits platelet function, with the exception of aspirin ≤ 150 mg per day or low molecular weight heparin.

Patient must not have history of platelet dysfunction, bleeding diathesis, and/or coagulopathy in the 6 months prior to screening;

Patient must not require treatment with any strong CYP3A4 inducer or inhibitor

Patient must not have history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes and their excipients;

Patients must not take other investigational drugs within 28 days prior to screening;

Patient must not be pregnant or lactating at screening and/or baseline;

Patient must not have impaired cardiac functions

Other protocol-defined inclusion/exclusion criteria may apply