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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Winship Cancer Institute
Atlanta, Georgia, United States
Dana Farber Cancer Institute.
Boston, Massachusetts, United States
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.
Time frame: Week 3 to week 6
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.
Time frame: Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days
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.
Time frame: Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
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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, United States
Local Institution
St Leonards, New South Wales, Australia
Local Institution
Adelaide, South Australia, Australia
Local Institution
Parkville, Victoria, Australia
QEII Health Sciences Centre-VG Site
Halifax, Nova Scotia, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
...and 11 more locations
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
Time frame: Up to 40 Months
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)
Time frame: Up to 40 Months
Incidence of Laboratory Abnormalities in Specific Thyroid Tests
Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
Time frame: Up to 40 Months
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).
Time frame: upto 36 Months
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).
Time frame: upto 36 Months
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).
Time frame: upto 36 Months
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).
Time frame: upto 36 Months
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).
Time frame: upto 36 Months
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).
Time frame: upto 36 Months
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.
Time frame: Up to 36 Months
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.
Time frame: Up to 36 Months
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.
Time frame: Up to 36 Months
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
Time frame: Up to 36 Months
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
Time frame: Up to 36 Months
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
Time frame: Up to 36 Months
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.
Time frame: Up to 36 Months
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.
Time frame: Up to 36 Months
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.
Time frame: Up to 36 Months
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
Time frame: Up to 36 Months
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
Time frame: Up to 36 Months
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
Time frame: Up to 36 Months