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Study Summary
No. 2007-0405:.......Leukemia......Guillermo Garcia-Manero......Leukemia
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Study Summary Title
Study Summary
Number:
2007-0405
Study Title:A PHASE 1, OPEN-LABEL, DOSE-ESCALATION STUDY 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)
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Physician New Patient Referral
Name:Guillermo Garcia-ManeroPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-745-3428
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:Celgene Corporation
Phase of Study:Phase IReturn
Visit:
During Cycle 1, participants will have 11 visits (Days 1-8 will be
consecutive), then visits will be weekly for 3 consecutive weeks. During Cycle
2, 6 visits, and during Cycles 3-7, 4 visits .
Treatment
Agents:
AzacytidineHome Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of an oral form (tablet or capsule) of azacitidine that is taken by mouth
(called oral azacitidine) that can be given to patients with MDS, CMML, or AML.
The safety of this drug will also be studied.

Researchers will also perform certain research tests during the study. Blood
will be drawn for pharmacodynamic (PD) testing. PD testing is used to look at
how the level of study drug in your body may affect the disease. Blood and
urine will be collected for pharmacokinetic (PK) testing. PK testing measures
the amount of study drug in the body at different time points. If you have a
bone marrow aspirate/biopsy, additional research tests will be conducted to
look at how the drug may affect your bone marrow.
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Study Objectives / Outcomes
Primary objectives are:
1. To determine the maximum tolerated dose (MTD)of oral azacitidine on different treatment schedules;
2. To determine dose limiting toxicities (DLTs) of oral azacitidine;
3. To determine the safety profile of oral azacitidine when administered to subjects with MDS, CMML or AML, as defined by World Health Organization (WHO) criteria;
4. To evaluate the pharmacokinetic (PK) behavior of azacitidine administered orally and SC; and
5. To evaluate the pharmacodynamic (PD) effects of azacitidine administered orally and SC.

Secondary objectives are:
1. To evaluate hematological response and/or improvement rate according to revised IWG criteria; and
2. To determine the biologically active dose (BAD) based on safety, PK, and PD data.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:08/24/2007
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:120
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male or female >/= 18 years of age.

2) Diagnosis of MDS, CMML or AML. For subjects with AML, eligibility is limited to those subjects for whom standard curative measures do not exist or are no longer effective.

3) Platelet count </= 50 x 10^9/L (</= 50,000/mu L), or hemoglobin </= 9.0 g/dL, or transfusion dependent.

4) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

5) Women of childbearing potential may participate, providing they meet the following conditions: Must agree to use at least 2 physician-approved contraceptive methods throughout the study and for 3 months following the last day of azacitidine dosing. Must have a negative serum pregnancy test obtained during screening within 7 days prior to azacitidine dosing on Cycle 1, Day 1.

6) Males with female partners of childbearing potential must agree to use at least 2 physician-approved contraceptive methods throughout the study and should avoid fathering a child for 3 months following the last day of azacitidine dosing.

7) Serum creatinine levels </= 2.5 x upper limit of normal (ULN).

8) Serum glutamic oxaloacetic transaminase (SGOT [AST]) and serum glutamic pyruvic transaminase (SGPT [ALT]) levels </= 2.5 x ULN.

9) Serum bilirubin levels </= 1.5 x ULN. Higher levels are acceptable if these can be attributed to active hemolysis (as indicated by positive direct Coomb's test, decreased haptoglobin, Gilbert's disease, elevated indirect bilirubin and/or lactate dehydrogenase [LDH]) or ineffective erythropoiesis (as indicated by bone marrow findings).

10) Serum bicarbonate >/= 20 mEq/L.

11) Written informed consent, willingness, and ability to comply with all study procedures.

Exclusion Criteria:1) A diagnosis of acute promyelocytic leukemia.

2) Previous or concurrent malignancy (other than MDS, CMML or AML) except adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.

3) Prior treatment with azacitidine or other demethylating agents.

4) Active, uncontrolled clinically significant infections.

5) Presence of serious illness, medical condition, or other medical history, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.

6) Any known or suspected hypersensitivity to azacitidine or mannitol or any other ingredient used in the manufacture of azacitidine drug product.

7) Presence of gastrointestinal disease or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.

8) Known Human Immunodeficiency Virus (HIV) or Hepatitis C, or known active viral Hepatitis B.

9) Breastfeeding or pregnant females.

10) Treatment with any anticancer therapy (standard or investigational) within the previous 21 days prior to the first dose of study drug or less than full recovery (CTCAE grade 1) from the clinically significant toxic effects of that treatment. The use of hydroxyurea in subjects with rapidly proliferating disease is allowed only during Cycle 1 after SC administration of azacitidine for 7 days for subjects in Part 1 only. Hydroxyurea may be used for two weeks after dosing in Cycle 1 (eg, Days 8-21 dosed with hydroxyurea) for subjects in Part 1 only.

11) Treatment with any investigational drugs within the previous 21 days prior to Cycle 1, Day 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period.

12) Current congestive heart failure (NY Heart Association Class III-IV), unstable angina or angina requiring surgical or medical intervention within 6 months prior to Cycle 1, Day 1, myocardial infarct within 6 months prior to Cycle 1, Day 1, or uncontrolled cardiac arrhythmia (defined as arrhythmia that is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia). Subjects with controlled atrial fibrillation that is asymptomatic are eligible.

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Links
Registration Number: NCT00528983
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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