Safety & Pharmacokinetics Study Of Azacitidine (SC And Oral) In Subjects With MDS, CMML, AML, Lymphoma And Multiple Myeloma

Multiple Myeloma Clinical Trial

— RACE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00761722
• Other study ID #: AZA PH US 2008 CL008
• Status: Completed
• Phase: Phase 1
• Start date: August 12, 2008
• Est. completion date: April 7, 2016

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: April 7, 2016
• Est. primary completion date: April 6, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Lymphoma
• Multiple Myeloma
• Myelodysplastic Syndromes
• Neoplasms, Plasma Cell
• Preleukemia
• Syndrome

Intervention

Drug:
• azacitidine
Arm 1: Cycle 1 (PK Phase) - Subjects will receive a single SC dose of 75 mg/m2 on Days 1 and 15. Single oral doses of a given formulation of azacitidine will be administered in increasing doses on Days 3 and 5, and at doses calculated to deliver 80% and 120% of the SC exposure, up to a maximum dose of 600 mg on Days 17 and 19. Cycles 2 and beyond - (Treatment phase) Oral azacitidine will be administered in a dose calculated to deliver 100% of the SC exposure up to a maximum of 600 mg on days 1 - 7 of a 28 day cycle. Arm 2: All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.

Locations

Country	Name	City	State
United States	Northwest Cancer Specialists, P.C.	Albuquerque	New Mexico
United States	California Cancer Care Inc	Greenbrae	California
United States	University of Texas- MD Anderson	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Main Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Hematology and Oncology Assoc. of South Texas	San Antonio	Texas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Willamette Valley Cancer Institute	Springfield	Oregon
United States	Yakima Valley Memorial Hospital/ North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		1 - 18 months
Secondary	To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation		1 - 18 months
Secondary	To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine		1 - 18 months
Secondary	To assess response rates		1 - 18 months
Secondary	To assess RBC transfusion independence		1 - 18 months
Secondary	To investigate the pharmacokinetics of oral azacitidine		1 -18 months
Secondary	To assess the pharmacodynamic effects of oral azacitidine		1 -18 months