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

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
azacitidine
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Myelodysplastic Syndromes, Lymphoma, Multiple Myeloma, Chronic Myelomonocytic Leukemia (CMML)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • California Cancer Care Inc
  • Main Cancer Centers of Florida, P.A.
  • Indiana University School of Medicine
  • University of Kansas Medical Center
  • Washington University School of Medicine
  • Northwest Cancer Specialists, P.C.
  • Willamette Valley Cancer Institute
  • University of Texas- MD Anderson
  • Hematology and Oncology Assoc. of South Texas
  • Fred Hutchinson Cancer Research Center
  • Yakima Valley Memorial Hospital/ North Star Lodge

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

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.

Oral Azacitidine All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
September 25, 2008
Last Updated
November 6, 2019
Sponsor
Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT00761722
Brief Title
Safety & Pharmacokinetics Study Of Azacitidine (SC And Oral) In Subjects With MDS, CMML, AML, Lymphoma And Multiple Myeloma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
August 12, 2008 (Actual)
Primary Completion Date
April 6, 2016 (Actual)
Study Completion Date
April 7, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Lymphoma, Multiple Myeloma, Leukemia, Myelomonocytic, Chronic
Keywords
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Lymphoma, Multiple Myeloma, Chronic Myelomonocytic Leukemia (CMML)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
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 Title
Arm 2
Arm Type
Experimental
Arm Description
Oral Azacitidine All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.
Intervention Type
Drug
Intervention Name(s)
azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Time Frame
1 - 18 months
Secondary Outcome Measure Information:
Title
To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation
Time Frame
1 - 18 months
Title
To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine
Time Frame
1 - 18 months
Title
To assess response rates
Time Frame
1 - 18 months
Title
To assess RBC transfusion independence
Time Frame
1 - 18 months
Title
To investigate the pharmacokinetics of oral azacitidine
Time Frame
1 -18 months
Title
To assess the pharmacodynamic effects of oral azacitidine
Time Frame
1 -18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barry Skikne, MD, FACP, FCP (SA)
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
California Cancer Care Inc
City
Greenbrae
State/Province
California
ZIP/Postal Code
94904
Country
United States
Facility Name
Main Cancer Centers of Florida, P.A.
City
Ocoee
State/Province
Florida
ZIP/Postal Code
34761
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Northwest Cancer Specialists, P.C.
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Willamette Valley Cancer Institute
City
Springfield
State/Province
Oregon
ZIP/Postal Code
97477
Country
United States
Facility Name
University of Texas- MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hematology and Oncology Assoc. of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-4417
Country
United States
Facility Name
Yakima Valley Memorial Hospital/ North Star Lodge
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24374798
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.
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Safety & Pharmacokinetics Study Of Azacitidine (SC And Oral) In Subjects With MDS, CMML, AML, Lymphoma And Multiple Myeloma

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