Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myelogenous Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00528983
First received: September 11, 2007
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to determine whether a tablet form of azacitidine that taken by mouth is safe. This Phase I study will also look at different doses and different treatment schedules in order to better understand the effects (positive and negative) of oral azacitidine on the body and on the disease MDS, AML and CMML.


Condition Intervention Phase
Myelodysplastic Syndromes (MDS)
Chronic Myelomonocytic Leukemia (CMML)
Acute Myelogenous Leukemia (AML)
Drug: Subcutaneous (SC) Azacitidine
Drug: Oral Azacitidine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I, Open-Label, Dose-Escalation Study to Evaluate the Safety, PK & PD of Oral Azacitidine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Safety evaluation as measured by monitoring AEs, dose limiting toxicities, scheduled lab assessments, vital sign measurements, ECGs, & physical exams for study duration. Adverse changes in physical signs/symptoms will be graded according to CTC AE V.3.0. [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]
  • Maximum-tolerated dose [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic blood and bone marrow samples will be collected and evaluated. [ Time Frame: 60 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy assessed by evidence of response (MDS subjects) and/or hematologic improvement (MDS subjects) examined using IWG criteria. [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Biologically active dose based on safety, PK and PD data. [ Time Frame: 60 months ] [ Designated as safety issue: No ]

Enrollment: 133
Study Start Date: September 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Subcutaneous (SC) Azacitidine and Oral Azacitidine
Cycle 1 subjects receive SC Azacitidine for first 7 days of 28 day cycle. For Cycle 2 and beyond subjects receive Oral Azacitidine (experimental) for first 7 days of 28 day cycle.
Drug: Subcutaneous (SC) Azacitidine
75 mg/day for first 7 days of 28 day cycle for 1 cycle only.
Other Name: Vidaza
Drug: Oral Azacitidine
Cycle 2 and beyond starting dose of 120 mg/day for first 7 days of 28 day cycle. Dose will escalate in increments of 60 mg. Following evaluation dose escalation will occur in 120 mg increments until maximum tolerated dose (MTD) is reached.
Other Name: CC-486
Experimental: Oral Azacitidine
Subjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle.
Drug: Oral Azacitidine
Starting dose for 14 day-QD treatment schedule will be 300 mg/day. Starting dose for 14 day-BID, 21 day-QD, 21 day-BID treatment schedules will be 100 mg, 200mg, 300mg. Dose will escalate in increments of 100 mg until MTD is reached.
Other Name: CC-486

Detailed Description:

Optional Extension Phase (OEP) to the AZA PH US 2007 CL 005 study which allows subjects who continue to receive oral azacitidine and have stable disease or are demonstrating clinical benefit as assessed by the Investigator, and have consented to participate, may enter the OEP of this study (at their current doses) at the start of their next cycle.

Subjects who are entering the OEP should be discontinued from Part 1 or Part 2 protocol prescribed therapy in the AZA PH US 2007 CL 005 study.

Subjects may continue to receive oral azacitidine in the OEP until they meet the criteria for study discontinuation or oral azacitidine becomes commercially available. Subjects discontinuing from the OEP will have an OEP discontinuation visit 28 days after the last dose of study drug or at study withdrawal.

Primary Objective of OEP is to evaluate long term safety of oral azacitidine.

  Eligibility

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

Inclusion Criteria:

  • 18 years or older.
  • Diagnosis of low or Int-1 risk MDS
  • Low platelet count, and/or low hemoglobin, and/or RBC transfusion-dependent and/or platelet transfusion-dependent
  • ECOG Performance status 0-2
  • Standard safety inclusion for serum creatinine, AST, ALT, bilirubin.
  • Serum bicarbonate greater than or equal to 20 mEq/L.
  • Use of acceptable birth control.
  • Signed, written informed consent.

Exclusion Criteria:

  • Diagnosis of acute PML.
  • Previous or concurrent malignancy.
  • Prior treatment with azacitidine or other demethylating agents.
  • Treatment with any anticancer therapy or investigational drugs within 21 days.
  • Hypersensitivity to azacitidine or mannitol.
  • Presence of GI disease.
  • Active, uncontrolled infection.
  • Known Human Immunodeficiency Virus (HIV) or Hepatitis C, or known active viral Hepatitis B.
  • Breastfeeding or Pregnant females;
  • Presence of serious illness, medical condition, or other medical history which would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
  • Current congestive heart failure (NY Heart Association Class III-IV), unstable angina or angina requiring surgical or medical intervention within 6 months, myocardial infarct within 6 months, or uncontrolled cardiac arrhythmia.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00528983

Locations
United States, Florida
Shands Cancer Center at the University of Florida
Gainesville, Florida, United States, 32610
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City VA Medical Center
Kansas City, Missouri, United States, 64128
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New York
New York Oncology Hematology P.C.
Albany, New York, United States, 12206
United States, Ohio
Gabrail Cancer Center Reearch
Canton, Ohio, United States, 44718
United States, South Carolina
Institute of Translational Oncology Research
Greenville, South Carolina, United States, 29605
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology Cancer Center
Austin, Texas, United States, 78731
MD Anderson - University of Texas
Houston, Texas, United States, 77030
Cancer Centers of South Texas - HOAST
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
North Star Lodge Cancer Center
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Barry Skikne, M.D., FACP; FCP (SA) Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00528983     History of Changes
Other Study ID Numbers: AZA PH US 2007 CL005
Study First Received: September 11, 2007
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Myelodysplastic Syndromes MDS
Acute Myelogenous Leukemia AML
Chronic Myelomonocytic Leukemia CMML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014