Phase I/II - Dasatinib and Decitabine

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01498445
First received: December 21, 2011
Last updated: May 1, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to learn if combining Spyrcel (dasatinib) and Dacogen (decitabine) can help to control 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.


Condition Intervention Phase
Leukemia
Drug: Dasatinib
Drug: Decitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) Dasatinib and Decitabine [ Time Frame: End of first 28-day cycle ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Hematologic Responses During First 3 months of Treatment [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Number of participants with hematologic response (HR) to therapy during first 3 months of combination dasatinib and decitabine therapy, where HR defined as any hematologic response observed during the first 3 months of treatment. Overall Hematologic Response (OHR) is defined as complete hematologic response (CHR), no evidence of leukemia (NEL) or minor hematologic response (MiHR)


Estimated Enrollment: 84
Study Start Date: June 2012
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib + Decitabine 10 mg/m2
Less Intensive, Schedule A Dasatinib starting dose of 100 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle.
Drug: Dasatinib
Starting Dose: 100 mg by mouth once daily of a 28 day cycle.
Other Names:
  • BMS-354825
  • Sprycel
Drug: Decitabine
Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.
Other Name: Dacogen
Experimental: Dasatinib + Decitabine 20 mg/m2
More Intensive, Schedule B: Dasatinib starting dose 100 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle.
Drug: Dasatinib
Starting Dose: 100 mg by mouth once daily of a 28 day cycle.
Other Names:
  • BMS-354825
  • Sprycel
Drug: Decitabine
Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.
Other Name: Dacogen

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. ECOG performance status 0-3.
  4. Men and women of childbearing potential should practice effective methods of contraception. 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.
  5. Women of childbearing potential must have a pregnancy test at screening.
  6. Signed informed consent.
  7. 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 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.
  8. Adequate organ function: Serum creatinine </= 2.0 mg/dl or creatinine clearance >/=60 mL/min; Total bilirubin </= 1.5 x ULN (unless considered due to Gilbert's syndrome or hemolysis); Alanine aminotransferase (ALT) </= 3 x ULN unless considered due to leukemic involvement.

Exclusion Criteria:

  1. NYHA cardiac class 3-4 heart disease.
  2. 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 both the Fridericia and Bazett'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.
  3. 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.
  4. Patients with known, clinically significant pericardial or pleural effusion.
  5. 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).
  6. Subject is receiving potent inhibitors of CYP3A4; for such medications, a wash-out period of >/= 7 days is required prior to starting dasatinib unless discontinuation or substitution of such an inhibitor is not in the best interest of the patient as determined by the investigator. These include the following medications: itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, isoniazid, ketamine, nefazodone, nicardipine, propofol, quinidine, telithromycin. In instances where use of these agents is felt to be required for the best management of the patients, inclusion of such a patients should be discussed with PI and the rationale documented.
  7. Females who are pregnant or are currently breastfeeding.
  8. Patients that are eligible (including having available donor) and willing to receive an allogeneic stem cell transplant within 4 weeks.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498445

Contacts
Contact: Jorge Cortes, MD 713-794-5783

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Jorge Cortes, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01498445     History of Changes
Other Study ID Numbers: 2011-0333, CA180357, NCI-2012-00014
Study First Received: December 21, 2011
Last Updated: May 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Chronic myelogenous leukemia
Chronic myeloid leukemia
CML
Accelerated phase
Blastic phase
Dasatinib
BMS-354825
Sprycel
Decitabine
Dacogen

Additional relevant MeSH terms:
Blast Crisis
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Pathologic Processes
Decitabine
Azacitidine
Dasatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014