A Study of Ruxolitinib in Combination With Nilotinib in Patients With Chronic Phase CML

Study Overview
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Brief Summary
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This study combines two drugs (ruxolitinib and the tyrosine kinase inhibitor, nilotinib) in an attempt to eliminate the CML (Chronic Myeloid Leukemia) stem cell population and thus allow for the deepest and most durable response possible in patients with CML in chronic phase who have achieved a complete hematologic remission (CHR), complete cytogenetic remission (CCyR), and major molecular remission (MMR), but not a complete molecular remission (CMR). The study will look at safety and tolerability of ruxolitinib when combined with nilotinib in a phase I study and will help establish the MTD (Maximum Tolerated Dose) of ruxolitinib when combined with nilotinib. Once the optimal dose of ruxolitinib is established in the phase I setting, a phase II evaluation will seek to establish the efficacy of this combination.

Official Title
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A Phase I/II Study of Ruxolitinib in Combination With Nilotinib in Patients With Chronic Phase CML Who Have Achieved a Complete Hematologic Remission, Complete Cytogenetic Remission, and Major Molecular Remission, But Not a Complete Molecular Remission on a Tyrosine Kinase Inhibitor Alone.

Conditions
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Leukemia, Chronic Myeloid

Intervention / Treatment
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* Drug: Nilotinib
* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age ECOG (Eastern Cooperative Oncology Group) Performance Status 0, 1, or 2 Must have a diagnosis of Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, with no previous evidence of accelerated or blast-phase disease. Must be actively receiving treatment for their CML with a tyrosine kinase inhibitor (TKI): imatinib, dasatinib, nilotinib or bosutinib, and must be on stable dose for > 1 year. Must have an ongoing complete hematologic response (CHR) on a TKI Must have an ongoing complete cytogenetic response (CCyR) on a TKI Must be in a major molecular remission (MMR) on a TKI for a minimum of 1 year leading up to enrollment. Adequate end organ function Adequate electrolytes Adequate platelet count Adequate neutrophil count Written informed consent prior to any screening procedures Exclusion Criteria: Patients in complete molecular remission (CMR) on a TKI. Patients who have failed nilotinib or not tolerated nilotinib in the past Certain cardiovascular disorders Currently receiving treatment with strong CYP3A4 inhibitors which cannot be discontinued prior to starting study drug Actively receiving herbal medicines that are strong CYP3A4 inhibitors and/or inducers and treatment cannot be discontinued prior to starting study drug Currently receiving treatment with any medications that have the potential to prolong the QT interval that cannot be discontinued prior to starting study drug Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the drug Acute or chronic pancreatic disease within the last year Cytopathologically confirmed Central Nervous System (CNS) infiltration Another primary malignancy that requires systemic chemotherapy or radiation Acute or chronic liver disease or severe renal disease considered unrelated to the cancer History of significant congenital or acquired bleeding disorder unrelated to cancer Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered from prior surgery Past treatment with ruxolitinib Treatment with other investigational agent within 30 days of Day 1 Inability to grant consent or history of non-compliance to medical regimens Women who are breastfeeding Women of child-bearing potential, unless they are using highly effective contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nilotinib + Ruxolitinib<br>The first part of the trial will be Phase I and will enroll 25 participants. Participants will receive nilotinib BID and either 10, 15 or 20 mg of ruxolitinib BID. Maximum tolerated dose (MTD) of ruxolitinib will be determined. The second part of the trial will be a Phase II and will enroll 25 subjects. Participants will receive nilotinib and the MTD of ruxolitinib. | Drug: Nilotinib<br>* Nilotinib 300 mg BID<br>Drug: Ruxolitinib<br>* Ruxolitinib, 10, 15 or 20mg BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib | Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib | 2 Years | 
| The number of patients that achieve a Complete Molecular Response (CMR) | CMR is defined as an absence of the BCR-ABL1 transcript by qPCR performed on peripheral blood or bone marrow aspirate. | 2 Years |