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Myelodysplastic Syndromes (MDS)Phase 1NCT00528983

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

A Phase 1 study testing Subcutaneous (SC) Azacitidine and Oral Azacitidine in people with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by Celgene at 18 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Subcutaneous (SC) Azacitidine and Oral Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
133 participants
Where
18 sitesUnited States
Study dates
11 Sep 2007to 5 Apr 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • New York Oncology Hematology P.C.

    Albany, New York, 12206

  • Texas Oncology Cancer Care

    Austin, Texas, 78731

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21231-1000

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Florida

    Gainesville, Florida, 32610-0277

  • Institute for Translational Oncology Research IRB

    Greenville, North Carolina, 29605

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Central Indiana Cancer Centers

    Indianapolis, Indiana, 46219

  • Kansas City VA Medical Center University of Kansas Medical Center

    Kansas City, Missouri, 64128

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • HOAST

    San Antonio, Texas, 78229

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109-4417

  • Kansas University Medical Center

    Westwood, Kansas, 66205

  • Yakima Valley Memorial Hospital/ North Star Lodge

    Yakima, Washington, 98902

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Subcutaneous (SC) Azacitidine, Oral Azacitidine
Keywords
Myelodysplastic Syndromes MDS, Acute Myelogenous Leukemia AML, Chronic Myelomonocytic Leukemia CMML
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Juvenile

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Subcutaneous (SC) AzacitidineDrug

    Also called Vidaza

    75 mg/day for first 7 days of 28 day cycle for 1 cycle only.

  • Oral AzacitidineDrug

    Also called CC-486

    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.

  • Oral AzacitidineDrug

    Also called CC-486

    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.

Study groups in NCT00528983
Study groupRoleWhat they receive
Subcutaneous (SC) Azacitidine and Oral AzacitidineExperimentalCycle 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.
Receives: Drug: Subcutaneous (SC) Azacitidine; Drug: Oral Azacitidine
Oral AzacitidineExperimentalSubjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle.
Receives: Drug: Oral Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 60 months

  2. Maximum-tolerated dose

    Measured: 60 months

  3. Pharmacodynamic blood and bone marrow samples will be collected and evaluated.

    Measured: 60 months

Secondary outcomes (2)

  1. Efficacy assessed by evidence of response (MDS subjects) and/or hematologic improvement (MDS subjects) examined using IWG criteria.

    Measured: 60 months

  2. Biologically active dose based on safety, PK and PD data.

    Measured: 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2007 (estimated)
  2. Study start11 Sep 2007
  3. Primary completion31 Jul 2013
  4. Study completion5 Apr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
133 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00528983
Sponsor's protocol ID
AZA PH US 2007 CL005
Status last verified
Nov 2019
First submitted
11 Sep 2007
Last updated
8 Nov 2019
Results posted
No
Data monitoring committee
No

Publications

  • Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, Laille E, Giordano H, Sakoian S, Jabbour E, Kantarjian H, Skikne B. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011 Jun 20;29(18):2521-7. doi: 10.1200/JCO.2010.34.4226. Epub 2011 May 16.

    PubMed 21576646

  • Garcia-Manero G, Gore SD, Kambhampati S, Scott B, Tefferi A, Cogle CR, Edenfield WJ, Hetzer J, Kumar K, Laille E, Shi T, MacBeth KJ, Skikne B. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016 Apr;30(4):889-96. doi: 10.1038/leu.2015.265. Epub 2015 Oct 7.

    PubMed 26442612

  • Laille E, Shi T, Garcia-Manero G, Cogle CR, Gore SD, Hetzer J, Kumar K, Skikne B, MacBeth KJ. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies. PLoS One. 2015 Aug 21;10(8):e0135520. doi: 10.1371/journal.pone.0135520. eCollection 2015.

    PubMed 26296092

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Subcutaneous (SC) Azacitidine and Oral Azacitidine in people with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by Celgene at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00528983, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2019.

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