Safety & Pharmacokinetics Study Of Azacitidine (SC And Oral) In Subjects With MDS, CMML, AML, Lymphoma And Multiple Myeloma (RACE)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Myeloid Leukemia Myelodysplastic Syndromes Lymphoma Multiple Myeloma Leukemia, Myelomonocytic, Chronic |
Drug: azacitidine |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1, Open-Label, Dose-Ranging Study To Evaluate The Pharmacokinetics and Safety of Azacitidine Administered Subcutaneously and as Different Oral Formulations In Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myelogenous Leukemia (AML), Lymphoma, and Multiple Myeloma(MM) |
- 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 ] [ Designated as safety issue: No ]
- To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation [ Time Frame: 1 - 18 months ] [ Designated as safety issue: No ]
- To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine [ Time Frame: 1 - 18 months ] [ Designated as safety issue: Yes ]
- To assess response rates [ Time Frame: 1 - 18 months ] [ Designated as safety issue: No ]
- To assess RBC transfusion independence [ Time Frame: 1 - 18 months ] [ Designated as safety issue: No ]
- To investigate the pharmacokinetics of oral azacitidine [ Time Frame: 1 -18 months ] [ Designated as safety issue: No ]
- To assess the pharmacodynamic effects of oral azacitidine [ Time Frame: 1 -18 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | September 2008 |
| Estimated Study Completion Date: | August 2012 |
| Estimated Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm 1
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. |
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. Other Name: Vidaza
|
|
Experimental: Arm 2
Oral Azacitidine All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle. |
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. Other Name: Vidaza
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Kansas | |
| Kansas University Medical Center | |
| Kansas City, Kansas, United States, 66160 | |
| United States, Texas | |
| Cancer Care Center of South Texas | |
| San Antonio, Texas, United States, 78229 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center | |
| Seattle, Washington, United States, 98109-1024 | |
| Northwest Cancer Specialists | |
| Vancouver, Washington, United States, 98684 | |
| North Star Lodge Cancer Center | |
| Yakima, Washington, United States, 98902 | |
| Study Director: | Jay Backstrom, M.D. | Celgene Corporation |
More Information
No publications provided
| Responsible Party: | Celgene Corporation |
| ClinicalTrials.gov Identifier: | NCT00761722 History of Changes |
| Other Study ID Numbers: | AZA PH US 2008 CL 008 |
| Study First Received: | September 25, 2008 |
| Last Updated: | February 2, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Celgene Corporation:
|
Acute Myeloid Leukemia Myelodysplastic Syndromes Lymphoma Multiple Myeloma Chronic Myelomonocytic Leukemia (CMML) |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelomonocytic, Chronic Lymphoma Multiple Myeloma Neoplasms, Plasma Cell Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms Myelodysplastic-Myeloproliferative Diseases Bone Marrow Diseases Hematologic Diseases Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hemorrhagic Disorders Precancerous Conditions Azacitidine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013