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

Phase 1

Completed

• Conditions: Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Lymphoma; Multiple Myeloma; Acute Myeloid Leukemia
• Interventions: Drug: azacitidine

• Registration Number: NCT00761722
• Lead Sponsor: Celgene

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08-12
• Study First Submitted: 2008-09-25
• Study First Submitted QC: 2008-09-26
• Study First Posted: 2008-09-29
• Primary Completion: 2016-04-06
• Study Completion: 2016-04-07
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-06
• Last Update Posted: 2019-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	azacitidine	subcutaneous and oral azacitidine 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	azacitidine	Oral Azacitidine All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation	1 - 18 months
To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine	1 - 18 months
To assess response rates	1 - 18 months
To assess RBC transfusion independence	1 - 18 months
To investigate the pharmacokinetics of oral azacitidine	1 -18 months
To assess the pharmacodynamic effects of oral azacitidine	1 -18 months

Trial Locations

Locations (11)

California Cancer Care Inc; 🇺🇸 Greenbrae, California, United States

Main Cancer Centers of Florida, P.A.; 🇺🇸 Ocoee, Florida, United States

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States

Northwest Cancer Specialists, P.C.; 🇺🇸 Albuquerque, New Mexico, United States

Hematology and Oncology Assoc. of South Texas; 🇺🇸 San Antonio, Texas, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Yakima Valley Memorial Hospital/ North Star Lodge; 🇺🇸 Yakima, Washington, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

University of Texas- MD Anderson; 🇺🇸 Houston, Texas, United States

Willamette Valley Cancer Institute; 🇺🇸 Springfield, Oregon, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States