A Phase 1B Study to Investigate the Safety and Preliminary Efficacy for the Combination of Dasatinib Plus Nivolumab in Patients With Chronic Myeloid Leukemia

Chronic Myeloid Leukemia Clinical Trial

Official title:

A Phase 1B Dose Escalation Study to Investigate the Safety, Tolerability and Preliminary Efficacy for the Combination Dasatinib (BMS-354825) Plus Nivolumab (BMS-936558) in Patients Chronic Myeloid Leukemia (CML)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02011945
• Other study ID #: CA180-373
• Secondary ID: 2013-002156-33
• Status: Completed
• Phase: Phase 1
• Start date: February 7, 2014
• Est. completion date: December 26, 2018

Study information

• Verified date: February 2020
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find a dose of Nivolumab that can be safely added to Dasatinib in patients with Chronic Myeloid Leukemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 26, 2018
• Est. primary completion date: December 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Confirmed diagnosis of Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase :

• With historically documented Ph+ cells

• =2 prior Tyrosine Kinase Inhibitors (TKI) therapies for CML

• Currently progressing, resistance to or with a suboptimal response to their most recent therapy

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score 0 - 1

Exclusion Criteria:

• Blast phase CML

• Known Abl-kinase mutation resistant to Dasatinib (e.g. T315I or T315A)

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Dasatinib

• Nivolumab

Locations

Country	Name	City	State
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Parkville	Victoria
Australia	Local Institution	St Leonards	New South Wales
Canada	QEII Health Sciences Centre-VG Site	Halifax	Nova Scotia
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	Local Institution	Bordeaux
Germany	Campus Virchow Klinikum Der Charite	Berlin
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Universitaetsklinikum Carl Gustav Carus	Dresden
Germany	Universitaetsklinik Frankfurt	Frankfurt am Main
Italy	Local Institution	Napoli
Italy	Local Institution	Orbassano
Italy	Local Institution	Roma
Spain	Local Institution	Madrid
Spain	Local Institution	Valencia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Dana Farber Cancer Institute.	Boston	Massachusetts
United States	Ut Southwestern Medical Center At Dallas	Dallas	Texas
United States	The University Of Texas MD Anderson Cancer Center	Houston	Texas
United States	Froedtert Hospital & Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLT)	DLT will be determined based on the incidence and intensity of drug related adverse events (AEs). The following drug-related AEs (whether related to one or both agents) occurring during the first 6 weeks of combined treatment with both dasatinib plus nivolumab (ie, Weeks 3 to 8, inclusive) would be considered DLTs: Grade 4 hematologic AE lasting > 7 days despite appropriate medical intervention, except as noted below; Grade 3 or Grade 4 nonhematologic AE irrespective of duration; Grade 2 nonhematologic AE lasting > 7 days despite appropriate medical intervention (exception: asymptomatic laboratory values of Grade 2 which do not require medical intervention); Any toxicity managed by discontinuation of nivolumab; Grade = 2 AE not controlled by medical intervention and requiring dasatinib treatment interruption for > 28 consecutive days; Grade = 2 AE not controlled by medical intervention and requiring missing 2 consecutive doses of nivolumab.	Week 3 to week 6
Primary	Incidence of Adverse Events (AEs)	Any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product.	Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days
Primary	Incidence of Serious Adverse Events (SAEs)	Any untoward medical occurrence that at any dose: results in death, is life threatening, requires in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a important medical event.Requires inpatient hospitalization or causes prolongation of existing hospitalization, results.	Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Primary	Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology	The number of participants with a shift in laboratory test results from baseline to Grade 3-4 in hematology	Up to 40 Months
Primary	Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests	The number of participants with an abnormal Liver function test.; Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)	Up to 40 Months
Primary	Incidence of Laboratory Abnormalities in Specific Thyroid Tests	Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)	Up to 40 Months
Secondary	Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants	Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR).; MMR is defined as = 3-log reduction in BCR-ABL transcripts or a ratio of = 0.1% on the International Scale (IS).	upto 36 Months
Secondary	Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants	Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR).; MMR is defined as = 3-log reduction in BCR-ABL transcripts or a ratio of = 0.1% on the International Scale (IS).	upto 36 Months
Secondary	Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants	Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR).; MMR is defined as = 3-log reduction in BCR-ABL transcripts or a ratio of = 0.1% on the International Scale (IS).	upto 36 Months
Secondary	Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants	Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR).; A molecular response 4.5 (MR4.5) was defined as = 4.5-log reduction in BCR-ABL transcripts or a ratio of = 0.00316% on the International Scale (IS).	upto 36 Months
Secondary	Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants	Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR).; A molecular response 4.5 (MR4.5) was defined as = 4.5-log reduction in BCR-ABL transcripts or a ratio of = 0.00316% on the International Scale (IS).	upto 36 Months
Secondary	Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants	Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR).; A molecular response 4.5 (MR4.5) was defined as = 4.5-log reduction in BCR-ABL transcripts or a ratio of = 0.00316% on the International Scale (IS).	upto 36 Months
Secondary	Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants	measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.	Up to 36 Months
Secondary	Time to Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants	measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.	Up to 36 Months
Secondary	Time to Major Molecular Response (MMR) - CML-AP Participants	measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.	Up to 36 Months
Secondary	Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants	will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment	Up to 36 Months
Secondary	Duration of Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants	will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment	Up to 36 Months
Secondary	Duration of Major Molecular Response (MMR) - CML-AP Participants	will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment	Up to 36 Months
Secondary	Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants	measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.	Up to 36 Months
Secondary	Time to Molecular Response 4.5(MR4.5) - CML-CP Prior Dasatinib Participants	measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.	Up to 36 Months
Secondary	Time to Molecular Response 4.5(MR4.5) - CML-AP Participants	measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.	Up to 36 Months
Secondary	Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants	will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment	Up to 36 Months
Secondary	Duration of Molecular Response 4.5 (MR4.5) - CML-CP Prior Dasatinib Participants	will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment	Up to 36 Months
Secondary	Duration of Molecular Response 4.5 (MR4.5) - CML-AP Participants	will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment	Up to 36 Months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form