NCT01751425

Ruxolitinib in Treating Participants With Chronic Myeloid Leukemia With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors

Phase I-II Study of Ruxolitinib (INCB18424) for Patients With Chronic Myeloid Leukemia (CML) With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of ruxolitinib and to see how well it works in participants with chronic myeloid leukemia with minimal residual disease while on therapy with tyrosine kinase inhibitors. Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of ruxolitinib and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML). (Phase I) II. To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML in complete cytogenetic remission (CCyR) with minimal residual disease (MRD). (Phase II) SECONDARY OBJECTIVES: I. To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML. (Phase I) II. To determine the safety of the combination of ruxolitinib and a TKI in patients with CML in CCyR with minimal residual disease. (Phase II) III. Determine the overall survival, event-free survival and survival free from transformation to accelerated and blast phase. (Phase I and II) IV. Determine the effect of therapy on bone marrow progenitors in clonogenic assays. (Phase I and II) V. Investigate the effect of therapy on molecular responses as assessed by genomic deoxyribonucleic acid (DNA) polymerase chain reaction (PCR). (Phase I and II) VI. Determine the effect of therapy on TKI-resistant quiescent leukemic Philadelphia chromosome (Ph)+ stem cells (CFSEmax/CD34+) by flow cytometric evaluation of activated Crkl and Jak2. (Phase I and II) VII. Assess the effect of therapy on self-renewal and/or survival of leukemic stem cells by fluorescence in situ hybridization (FISH) analysis on colonies. (Phase I and II) VIII. Assess ruxolitinib pharmacokinetics (PK) in preselected time intervals during co-administration of this agent with TKIs. (Phase I and II) OUTLINE: This is a phase I, dose-escalation study of ruxolitinib followed by a phase II study. Participants receive commercially available TKIs (imatinib mesylate, nilotinib, or dasatinib) as they had been receiving during the last 6 months and ruxolitinib orally (PO) twice daily (BID). Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up for 30 days.

Conditions

• Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission
• Minimal Residual Disease
• Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia

Interventions

Type	Name	Description
DRUG	Dasatinib	Given PO
DRUG	Imatinib Mesylate	Given PO
DRUG	Nilotinib	Given PO
DRUG	Ruxolitinib	Given PO

Timeline

• Start date: 2013-07-24
• Primary completion: 2019-09-24
• Completion: 2019-09-24
• First posted: 2012-12-18
• Last updated: 2025-06-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study