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

November 6, 2019 updated by: Celgene

A Phase 1, Open-label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myelogenous Leukemia (AML).

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

133

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610-0277
        • University of Florida
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46219
        • Central Indiana Cancer Centers
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Kansas University Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-1000
        • Johns Hopkins Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64128
        • Kansas City VA Medical Center University of Kansas Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Albany, New York, United States, 12206
        • New York Oncology Hematology P.C.
    • North Carolina
      • Greenville, North Carolina, United States, 29605
        • Institute for Translational Oncology Research IRB
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology Cancer Care
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • HOAST
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates
    • Washington
      • Seattle, Washington, United States, 98109-4417
        • Fred Hutchinson Cancer Research Center
      • Yakima, Washington, United States, 98902
        • Yakima Valley Memorial Hospital/ North Star Lodge

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • CC-486
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 Names:
  • 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
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 Names:
  • CC-486
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 Names:
  • CC-486

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
60 months
Maximum-tolerated dose
Time Frame: 60 months
60 months
Pharmacodynamic blood and bone marrow samples will be collected and evaluated.
Time Frame: 60 months
60 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Efficacy assessed by evidence of response (MDS subjects) and/or hematologic improvement (MDS subjects) examined using IWG criteria.
Time Frame: 60 months
60 months
Biologically active dose based on safety, PK and PD data.
Time Frame: 60 months
60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 11, 2007

Primary Completion (ACTUAL)

July 31, 2013

Study Completion (ACTUAL)

April 5, 2016

Study Registration Dates

First Submitted

September 11, 2007

First Submitted That Met QC Criteria

September 12, 2007

First Posted (ESTIMATE)

September 14, 2007

Study Record Updates

Last Update Posted (ACTUAL)

November 8, 2019

Last Update Submitted That Met QC Criteria

November 6, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AZA PH US 2007 CL005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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