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

Sponsor
University of Michigan Rogel Cancer Center (Other)
Overall Status
Withdrawn
CT.gov ID
NCT02973711
Collaborator
(none)
0
Enrollment
2
Locations
1
Arm
43
Anticipated Duration (Months)
0
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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.
Anticipated Study Start Date :
Jan 1, 2018
Anticipated Primary Completion Date :
Aug 1, 2021
Anticipated Study Completion Date :
Aug 1, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nilotinib + Ruxolitinib

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
Nilotinib 300 mg BID

Drug: Ruxolitinib
Ruxolitinib, 10, 15 or 20mg BID

Outcome Measures

Primary Outcome Measures

  1. Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib [2 Years]

    Maximum Tolerated Dose (MTD) of ruxolitinib when combined with nilotinib

  2. The number of patients that achieve a Complete Molecular Response (CMR) [2 Years]

    CMR is defined as an absence of the BCR-ABL1 transcript by qPCR performed on peripheral blood or bone marrow aspirate.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1The University of Michigan Comprehensive Cancer CenterAnn ArborMichiganUnited States48109
2Wake Forest University Health SciencesWinston-SalemNorth CarolinaUnited States27157

Sponsors and Collaborators

  • University of Michigan Rogel Cancer Center

Investigators

  • Principal Investigator: Patrick Burke, M.D., University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier:
NCT02973711
Other Study ID Numbers:
  • UMCC 2015.103
  • HUM00122063
First Posted:
Nov 25, 2016
Last Update Posted:
Feb 16, 2021
Last Verified:
Feb 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 16, 2021