Clinical trial NCT00761722: Safety & Pharmacokinetics Study Of Azacitidine (SC And Oral) In Subjects With MDS, CMML, AML, Lymphoma And Multiple Myeloma
Official title: A Phase I, Dose-Ranging Study to Evaluate the Pharmacokinetics and Safety of Azacitidine Administered Subcutaneously (SC) and as Different Oral Formulations in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myelogenous Leukemia (AML), Lymphoma, and Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Lymphoma
Multiple Myeloma
Leukemia, Myelomonocytic, Chronic
Keywords: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Lymphoma
Multiple Myeloma
Chronic Myelomonocytic Leukemia (CMML)
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2008-09-29
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the amount of drug that gets into the bloodstream between different tablets taken by mouth and an injection under the skin.


Eligibility criteria: Inclusion Criteria:

* 18 years or older
* Diagnosis of MDS or CMML
* Diagnosis of AML, Multiple myeloma, Hodgkin's or Non-Hodgkin's lymphoma for whom standard curative or palliative measures do not exist or are no longer effective
* ECOG Performance Status 0-2
* Use of acceptable birth control
* Standard safety inclusion for serum creatinine, AST, ALT, bilirubin
* Serum bicarbonate greater than or equal to 20 mEq/L
* Platelet count greater than or equal to 25,000/uL
* Hemoglobin greater than or equal to 500/uL
* Signed informed consent

Exclusion Criteria:

* Diagnosis of acute promyelocytic leukemia
* Treatment with demethylating agents within 21 days prior to Cycle 1, Day 1
* Treatment with any anticancer therapy (standard or investigational) within 21 days prior to Cycle 1, Day 1 or ongoing adverse events from previous treatment
* Hypersensitivity to azacitidine or mannitol
* Active, uncontrolled infection
* Presence of GI disease, malignant tumors or other conditions known to interfere with ADME
* Known or active HIV, viral hepatitis B or C
* Breastfeeding or pregnant females
* Current or uncontrolled cardiac disease

Primary outcomes:
measure: To estimate the dose for a given oral formulation that would yield similar exposure [area under the curve (AUC)] to 75 mg/m2 of the subcutaneous formulation.
timeFrame: 1 - 18 months
Secondary outcomes:
measure: To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation
timeFrame: 1 - 18 months
measure: To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine
timeFrame: 1 - 18 months
measure: To assess response rates
timeFrame: 1 - 18 months
measure: To assess RBC transfusion independence
timeFrame: 1 - 18 months
measure: To investigate the pharmacokinetics of oral azacitidine
timeFrame: 1 -18 months
measure: To assess the pharmacodynamic effects of oral azacitidine
timeFrame: 1 -18 months
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: California Cancer Care Inc
state: California
city: Ocoee
country: United States
facility: Main Cancer Centers of Florida, P.A.
state: Florida
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Albuquerque
country: United States
facility: Northwest Cancer Specialists, P.C.
state: New Mexico
city: Springfield
country: United States
facility: Willamette Valley Cancer Institute
state: Oregon
city: Houston
country: United States
facility: University of Texas- MD Anderson
state: Texas
city: San Antonio
country: United States
facility: Hematology and Oncology Assoc. of South Texas
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/ North Star Lodge
state: Washington
Study officials:
affiliation: Celgene Corporation
name: Barry Skikne, MD, FACP, FCP (SA)
role: STUDY_DIRECTOR
References:
citation: Laille E, Savona MR, Scott BL, Boyd TE, Dong Q, Skikne B. Pharmacokinetics of different formulations of oral azacitidine (CC-486) and the effect of food and modified gastric pH on pharmacokinetics in subjects with hematologic malignancies. J Clin Pharmacol. 2014 Jun;54(6):630-9. doi: 10.1002/jcph.251. Epub 2014 Jan 18.