Trial Outcomes & Findings for Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (NCT NCT02819804)

NCT ID: NCT02819804

Last Updated: 2020-02-11

Results Overview

Determine the maximum tolerated dose (MTD) of nivolumab when given in combination with dasatinib, the MTD will be defined as the highest dose level at which ≤ 1 DLT occurs and will be assessed by the Common Terminology Criteria for Adverse Events version 4.03.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

1 participants

Primary outcome timeframe

Up to 28 days

Results posted on

2020-02-11

Participant Flow

The study was activated for accrual on August 24, 2016 with the first patient enrolled and treated on the study on August 17, 2017. The study was terminated before the accrual goal of 22 patients was reached due to funding issues and slow accrual.

Participant milestones

Participant milestones
Measure	Treatment (Dasatinib, Nivolumab) Patients receive dasatinib PO QD on days 1-28 and nivolumab IV over 30 minutes on days 8 and 22 of course 1 and on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dasatinib: Given PO Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV Pharmacological Study: Correlative studies
Complete Cycle 1 (28 Days) STARTED	1
Complete Cycle 1 (28 Days) COMPLETED	0
Complete Cycle 1 (28 Days) NOT COMPLETED	1
Start Cycle 2 and Beyond STARTED	0
Start Cycle 2 and Beyond COMPLETED	0
Start Cycle 2 and Beyond NOT COMPLETED	0
Follow-up for 1 Year STARTED	1
Follow-up for 1 Year COMPLETED	1
Follow-up for 1 Year NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Dasatinib, Nivolumab) Patients receive dasatinib PO QD on days 1-28 and nivolumab IV over 30 minutes on days 8 and 22 of course 1 and on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dasatinib: Given PO Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV Pharmacological Study: Correlative studies
Complete Cycle 1 (28 Days) Progressive disease/no response	1

Baseline Characteristics

Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Dasatinib, Nivolumab) n=1 Participants Patients receive dasatinib PO QD on days 1-28 and nivolumab IV over 30 minutes on days 8 and 22 of course 1 and on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dasatinib: Given PO Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV Pharmacological Study: Correlative studies
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 28 days

Population: Only one patient was treated on study and this patient did not complete the DLT period and was not evaluable for this outcome measure or any of the outcome measures. Sample size too small for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 28-days after the last dose

To evaluate the toxicity and safety of nivolumab and dasatinib in patients with relapsed/refractory Ph+ ALL. Adverse events will be assessed by number, frequency, and severity and will be graded according to the NCI's common terminology criteria, version 4.03.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 84 days (3 cycles)

Determine the rate of complete hematologic remission (CR) after three cycles of nivolumab and dasatinib

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 84 days (3 cycles)

Determine the rate of molecular remission after three cycles of nivolumab and dasatinib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 hours after the start of cycle 1 and days 8, 15, and 22 prior to treatment during cycle 1

The serum level of dasatinib will be measured at 24 hours after the start of cycle 1 and on days 8, 15, and 22 prior to treatment during cycle 1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 8, 15, and 22 prior to treatment during cycle 1

The serum level of nivolumab will be measured on days 8, 15, and 22 prior to treatment during cycle 1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 28-days after the last dose

Peripheral blood will be evaluated to measure PD1 expression levels and saturation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 28-days after the last dose

Bone marrow will be assessed to measure PD1 expression levels and saturation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At cycle 1 days: 1, 2, 8, 15, & 22 prior to dosing

T-cell levels and activation will be measured in the peripheral blood after treatment.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 30 days

Number and percentage of patients that die within the first 30 days of initiating treatment.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

OS is defined as the time from the initiation of study treatment until death from any cause, evaluated for up to 1 year.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

PFS is defined as the time from the initiation of study treatment until the time of disease progression or relapse.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

Duration of remission is defined as the time from achieving complete response until the time of disease relapse.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 28-days after the last dose

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Dasatinib, Nivolumab)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Dasatinib, Nivolumab) n=1 participants at risk Patients receive dasatinib PO QD on days 1-28 and nivolumab IV over 30 minutes on days 8 and 22 of course 1 and on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dasatinib: Given PO Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV Pharmacological Study: Correlative studies
Blood and lymphatic system disorders Febrile Neutropenia	100.0% 1/1 • Number of events 1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).

Other adverse events

Other adverse events
Measure	Treatment (Dasatinib, Nivolumab) n=1 participants at risk Patients receive dasatinib PO QD on days 1-28 and nivolumab IV over 30 minutes on days 8 and 22 of course 1 and on days 1 and 15 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Dasatinib: Given PO Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV Pharmacological Study: Correlative studies
Metabolism and nutrition disorders Hypocalcemia	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Metabolism and nutrition disorders Hyperglycemia	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations White blood cell decreased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Neutrophil count decreased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Infections and infestations Papulopustular rash	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Vascular disorders Hypertension	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Alanine aminotransferase increased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Vascular disorders Hypotension	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Lipase increased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Infections and infestations Sepsis	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Gastrointestinal disorders Abdominal pain	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Blood and lymphatic system disorders Febrile neutropenia	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Lymphocyte count decreased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations INR increased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Metabolism and nutrition disorders Hyponatremia	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Alkaline phosphatase increased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Aspartate aminotransferase increased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Blood bilirubin increased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Injury, poisoning and procedural complications Fall	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Blood and lymphatic system disorders Anemia	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
Investigations Platelet count decreased	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).
General disorders Fatigue	100.0% 1/1 • The patient was monitored for AEs during treatment on the study and for 30 days after the last dose of study treatment (for approximately 40 days in duration).

Additional Information

Shira Dinner, MD

Northwestern University

Phone: 312-695-6180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place