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

NCT02973711 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: UMCC 2015.103HUM00122063
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Leukemia, Chronic Myeloid

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

Nilotinib + Ruxolitinib

EXPERIMENTAL

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; Drug: Ruxolitinib

Interventions

Nilotinib DRUG

Nilotinib 300 mg BID

Nilotinib + Ruxolitinib

Ruxolitinib DRUG

Ruxolitinib, 10, 15 or 20mg BID

Nilotinib + Ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (2)

The University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib; ruxolitinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Patrick Burke, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: November 25, 2016
• Study Start: January 1, 2018
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: February 16, 2021

Record last verified: 2021-02

Locations

US (2)