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

NCT ID: NCT00528983

Last Updated: 2019-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

133 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-09-11

Study Completion Date

2016-04-05

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Myelodysplastic Syndromes (MDS) Chronic Myelomonocytic Leukemia (CMML) Acute Myelogenous Leukemia (AML)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Subcutaneous (SC) Azacitidine

Intervention Type DRUG

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

Oral Azacitidine

Intervention Type DRUG

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 Azacitidine

Subjects receive Oral Azacitidine (experimental) QD or BID for the first 14 or 21 days of 28 day cycle.

Group Type EXPERIMENTAL

Oral Azacitidine

Intervention Type DRUG

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.

Interventions

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Subcutaneous (SC) Azacitidine

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

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Vidaza CC-486 CC-486

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Barry Skikne, M.D., FACP; FCP (SA)

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

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University of Florida

Gainesville, Florida, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Central Indiana Cancer Centers

Indianapolis, Indiana, United States

Site Status

Kansas University Medical Center

Westwood, Kansas, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Kansas City VA Medical Center University of Kansas Medical Center

Kansas City, Missouri, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

New York Oncology Hematology P.C.

Albany, New York, United States

Site Status

Institute for Translational Oncology Research IRB

Greenville, North Carolina, United States

Site Status

Gabrail Cancer Center

Canton, Ohio, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Texas Oncology Cancer Care

Austin, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

HOAST

San Antonio, Texas, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Yakima Valley Memorial Hospital/ North Star Lodge

Yakima, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21576646 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26442612 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26296092 (View on PubMed)

Other Identifiers

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AZA PH US 2007 CL005

Identifier Type: -

Identifier Source: org_study_id

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