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

NCT02011945 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CA180-3732013-002156-33
• Study Type: interventional
• Target: 35
• Locations: 7 countries
• Sites: 21

Brief 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.

Conditions

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• Incidence of Laboratory Abnormalities in Specific Thyroid Tests

  Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)

  Up to 40 Months

Secondary Outcomes (18)

• Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants

  upto 36 Months

• Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants

  upto 36 Months

• Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants

  upto 36 Months

• Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants

  upto 36 Months

• Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants

  upto 36 Months

Study Arms (3)

dasatinib Only

EXPERIMENTAL

dasatinib 100 mg QD(CP) or 140 mg QD (AP)

Drug: Dasatinib

Dose Level 1

EXPERIMENTAL

Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

Drug: Dasatinib; Drug: Nivolumab

Dose Level 2

EXPERIMENTAL

Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

Drug: Dasatinib; Drug: Nivolumab

Interventions

Dasatinib DRUG

Also known as: BMS-354825

Dose Level 1; Dose Level 2; dasatinib Only

Nivolumab DRUG

Also known as: BMS-936558

Dose Level 1; Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (21)

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Dana Farber Cancer Institute.

Boston, Massachusetts, 02215, United States

Location

Ut Southwestern Medical Center At Dallas

Dallas, Texas, 75390, United States

Location

The University Of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Froedtert Hospital & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Local Institution

St Leonards, New South Wales, 2065, Australia

Location

Local Institution

Adelaide, South Australia, 5000, Australia

Location

Local Institution

Parkville, Victoria, 3050, Australia

Location

QEII Health Sciences Centre-VG Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Local Institution

Bordeaux, 33000, France

Location

Campus Virchow Klinikum Der Charite

Berlin, 13353, Germany

Location

Universitaetsklinikum Bonn

Bonn, 53127, Germany

Location

Universitaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitaetsklinik Frankfurt

Frankfurt am Main, 60590, Germany

Location

Local Institution

Napoli, 80131, Italy

Location

Local Institution

Orbassano, 10043, Italy

Location

Local Institution

Roma, 00161, Italy

Location

Local Institution

Madrid, 28047, Spain

Location

Local Institution

Valencia, 46010, Spain

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Dasatinib; Nivolumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers squibb

Clinical.Trials@BMS.com

Please Email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2013
• First Posted: December 16, 2013
• Study Start: February 7, 2014
• Primary Completion: December 26, 2018
• Study Completion: December 26, 2018
• Last Updated: March 18, 2020
• Results First Posted: January 17, 2019

Record last verified: 2020-02

Locations

US (5); FR (1); DE (4); CA (3); AU (3); IT (3); ES (2)