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

Primary Purpose

Leukemia, Chronic Myeloid

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Nilotinib

Ruxolitinib

About this trial

This is an interventional treatment trial for Leukemia, Chronic Myeloid

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The University of Michigan Comprehensive Cancer Center
Wake Forest University Health Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nilotinib + Ruxolitinib

Arm Description

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.

Outcomes

Primary Outcome Measures

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

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02973711

First Posted

November 22, 2016

Last Updated

February 11, 2021

Sponsor

University of Michigan Rogel Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT02973711

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Withdrawn

Why Stopped

lack of funding

Study Start Date

January 2018 (Anticipated)

Primary Completion Date

August 2021 (Anticipated)

Study Completion Date

August 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Chronic Myeloid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nilotinib + Ruxolitinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Nilotinib

Intervention Description

Nilotinib 300 mg BID

Intervention Type

Drug

Intervention Name(s)

Ruxolitinib

Intervention Description

Ruxolitinib, 10, 15 or 20mg BID

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

2 Years

Title

The number of patients that achieve a Complete Molecular Response (CMR)

Description

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

Time Frame

2 Years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patrick Burke, M.D.

Organizational Affiliation

University of Michigan Rogel Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Michigan Comprehensive Cancer Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Wake Forest University Health Sciences

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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