An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)

NCT01498445 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: 2011-0333CA180357NCI-2012-00014
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if combining Sprycel (dasatinib) and Dacogen (decitabine) can help to control Chronic Myeloid Leukemia (CML). The dose level of decitabine will also be studied. Dasatinib is designed to block the protein that is responsible for chronic myeloid leukemia. Decitabine is designed to affect the mechanism that cells use to control the expression of certain genes, some of which are important in the progression of CML. This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of patients with certain types of CML. Decitabine is FDA approved for the treatment of patients with myelodysplastic syndrome. The combination of these drugs to treat CML is investigational. Up to 84 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions

Leukemia

Keywords

Leukemia; Chronic myelogenous leukemia; Chronic myeloid leukemia; CML; Accelerated phase; Blastic phase; Dasatinib; BMS-354825; Sprycel; Decitabine; Dacogen

Outcome Measures

Primary Outcomes (1)

• Ph I Study: Maximum Tolerated Dose (MTD) Dasatinib

  Maximum tolerated dose (MTD) defined as highest dose at which 0 of 3 or \</= 1/6 participant experience a first cycle dose limiting toxicity (DLT).

  End of first 28-day cycle

Secondary Outcomes (3)

• Number of Participants With Hematologic Responses During First 3 Months of Treatment

  3 months

• Overall Survival

  Up to seven years

• Duration of Response

  up to seven years

Study Arms (6)

Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2

EXPERIMENTAL

Less Intensive, Schedule A1 Dasatinib 100 mg daily by mouth ; Decitabine 10 mg/m\^2 by vein over 1 hour daily for 10 days; 28 day cycle.

Drug: Dasatinib; Drug: Decitabine

Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2

EXPERIMENTAL

More Intensive, Schedule A2: Dasatinib 100 mg daily by mouth ; Decitabine ose 20 mg/m\^2 by vein over 1 hour daily for 10 days; 28 day cycle.

Drug: Dasatinib; Drug: Decitabine

Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2

EXPERIMENTAL

Less Intensive, Schedule B1 Dasatinib 140 mg daily by mouth ; Decitabine 10 mg/m\^2 by vein over 1 hour daily for 10 days; 28 day cycle.

Drug: Dasatinib; Drug: Decitabine

Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2

EXPERIMENTAL

More Intensive, Schedule B2 Dasatinib 140 mg daily by mouth ; Decitabine 20 mg/m\^2 by vein over 1 hour daily for 10 days; 28 day cycle.

Drug: Dasatinib; Drug: Decitabine

Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2

EXPERIMENTAL

Less Intensive, Schedule B1 Dasatinib 140 mg daily by mouth; Decitabine e 10 mg/m\^2 by vein over 1 hour daily for 10 days; 28 day cycle.

Drug: Dasatinib; Drug: Decitabine

Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2

EXPERIMENTAL

More Intensive, Schedule B2 Dasatinib140 mg daily by mouth; Decitabine 20 mg/m\^2 by vein over 1 hour daily for 10 days; 28 day cycle.

Drug: Dasatinib; Drug: Decitabine

Interventions

Dasatinib DRUG

Starting Dose: 100 mg by mouth once daily of a 28 day cycle.

Also known as: BMS-354825, Sprycel

Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2; Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2; Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2; Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2; Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2; Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2

Decitabine DRUG

Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.

Also known as: Dacogen

Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2; Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2; Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2

Eligibility Criteria

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

You may qualify if:

• Patients age 18 years of age or older with CML-AP, CML-BP or Philadelphia chromosome-positive acute myeloid leukemia defined as follows: CML-AP is defined by the presence of 15-29% blasts in peripheral blood (PB) or bone marrow (BM), \>/= 20% basophils in PB or BM, \>/= 30% blasts plus promyelocytes (with blasts \<30%) in PB or BM, \<100 x10(9)/L platelets unrelated to therapy, or by clonal cytogenetics evolution (i.e., the presence of cytogenetic abnormalities other than the Philadelphia chromosome); CML-BP is defined by the presence of \>/= 30% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease.
• Patients are eligible whether they have received or not prior TKI therapy. For the phase I portion of the study, patients who had received prior therapy with dasatinib should have been able to tolerate the dose equivalent to the starting dose of dasatinib in the dose level at which the patient is being entered. Patients who previously received dasatinib but never at the dose being proposed are eligible provided they tolerated the maximum dose they were prescribed with no grade 3-4 toxicity not responding to optimal management.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
• Men and women of childbearing potential should practice 2 methods of contraception; 1 method must be highly effective and a second method must be either highly effective or less effective. Men and women of childbearing potential are defined as: a male that has not been surgically sterilized or a female that has not been amenorrheic for at least 12 consecutive months or that has not been surgically sterilized. Patients must use birth control during the study and for 3 months after the last dose of study drug if they are sexually active.
• Women of childbearing potential must have a pregnancy test at screening.
• Signed informed consent.
• Patients must have been off all prior therapy for CML for 2 weeks prior to start of study therapy and recovered from the toxic effects of that therapy. Exceptions to these are hydroxyurea and Tyrosine kinase inhibitor (TKIs) (including but not limited to imatinib, nilotinib, and bosutinib) which should be discontinued \>/= 24 hrs prior to the start of therapy. Patients who are receiving dasatinib prior to enrollment do not have to discontinue this agent prior to start of study therapy.
• Adequate organ function: Serum creatinine \</= 2.0 mg/dl or creatinine clearance \>/=60 mL/min; Total bilirubin \</= 1.5 x upper limit of normal (ULN) (unless considered due to Gilbert's syndrome or hemolysis); Alanine aminotransferase (ALT) \</= 3 x ULN unless considered due to leukemic involvement.

You may not qualify if:

• New York Heart Association (NYHA) cardiac class 3-4 heart disease.
• Cardiac disease including: Uncontrolled angina within 3 months. Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (\> 470 msec) on the Fridericia's correction; Uncontrolled hypertension (defined for this protocol as sustained systolic BP \>/=150 and diastolic \>/=100); Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes.
• Serious uncontrolled medical disorder or uncontrolled active systemic infection or current unstable or decompensated respiratory or cardiac conditions which makes it undesirable or unsafe for the patient to participate in the study.
• Patients with known, clinically significant pericardial or pleural effusion.
• History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), or diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies).
• Females who are pregnant or are currently breastfeeding.
• Patients that are eligible (including having available donor) and willing to receive an allogeneic stem cell transplant within 4 weeks.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis

Interventions

Dasatinib; Decitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Jorge Cortes MD/Professor
• Organization: The University of Texas MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 21, 2011
• First Posted: December 23, 2011
• Study Start: June 12, 2012
• Primary Completion: September 24, 2019
• Study Completion: September 24, 2019
• Last Updated: October 22, 2020
• Results First Posted: October 22, 2020

Record last verified: 2020-09

Locations

US (1)