Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function

NCT ID: NCT00652626

Last Updated: 2019-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-01
• Study Completion Date: 2012-07-01

Brief Summary

The purpose of this study is to evaluate three things. The first being whether azacitidine is absorbed in the body at the same rate or proportion for different concentrations. The second is to determine the effect renal impairment has or does not have on the absorption of azacitidine. The third is to determine if azacitidine is safe and well tolerated in patients with renal function impairment.

Conditions

MDS; AML; Solid Tumors; Multiple Myeloma; Non-Hodgkin's Lymphoma; Hodgkin's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Azacitidine 25 mg/m^2

Participants with normal renal function received a single subcutaneous dose of azacitidine 25 mg/m\^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m\^2 daily on Days 1-7 of each 28-day cycle.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Azacitidine 50 mg/m^2

Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m\^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m\^2 daily on Days 1-7 of each 28-day cycle.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Azacitidine 75 mg/m^2

Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m\^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m\^2 daily on Days 1-7 of each 28-day cycle.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Azacitidine 100 mg/m^2

Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m\^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m\^2 daily on Days 1-7 of each 28-day cycle.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Severe RI: azacitidine 75 mg/m^2

Participants with severe renal impairment (RI; defined as creatinine clearance \< 30 mL/min/1.73 m\^2) received subcutaneous doses of azacitidine 75 mg/m\^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m\^2 daily on Days 1-7 of each 28-day cycle.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Interventions

azacitidine

Intervention Type: DRUG

Other Intervention Names

Vidaza

Eligibility Criteria

Inclusion Criteria

• Diagnosis of one of the following:

• MDS according to the French-American-British (FAB) classification system: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), or chronic myelomonocytic leukemia (CMML); or
• Acute myelogenous leukemia (AML) in remission,
• Malignant solid tumor,
• Multiple myeloma (MM),
• Non-Hodgkin lymphoma (NHL), or
• Hodgkin lymphoma (HD)
• Patients with a history of treated brain metastases should be clinically stable for greater than 4 weeks prior to signing the informed consent form and off glucocorticoid therapy for central nervous system (CNS) edema for at least 4 weeks
• Be capable of giving informed consent
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Have a life expectancy ≥ 3 months
• Have stable renal function for at least 2 months
• Have average calculated creatinine clearance of:

• >80 mL/min/1.73m^2 for Cohorts 1, 2, 3, and 4
• <30 mL/min/1.73m^2 for Cohort 5 - Severe renal impairment,
• 50-80 mL/min/1.73m^2 for Cohort 6 - Mild renal impairment,
• 30 to <50 mL/min/1.73m^2 for Cohort 7 - Moderate renal impairment
• Have organ and marrow function at the screening and pre-dose visits as defined below:

• Hemoglobin ≥8 g/dL,
• Absolute neutrophil count ≥0.75 x 10^3/µL,
• Platelets ≥30 x 10^3/µL,
• Total bilirubin ≤1.5 times the upper limit of normal (ULN),
• Aspartate aminotransferase (AST) ≤2 times the ULN, and
• Alanine transaminase (ALT) ≤2 times the ULN;
• Have a 12-lead electrocardiogram (ECG) that is not clinically significant, as determined by the Investigator, at screening
• Have serum bicarbonate:

• 20 mEq/L for patients with normal renal function (cohorts 1, 2, 3 and 4),
• 16 mEq/L for patients with impaired renal function (cohorts 5, 6 and 7)
• Women of childbearing potential may participate, providing are not pregnant and agree to use at least 2 effective contraceptive methods throughout the study
• Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and to avoid fathering a child for 6 months following the date of the last dose of study medication
• Be a nonsmoker or must not have smoked for at least 30 days before the screening visit and agree to abstain from smoking during study participation

Exclusion Criteria

• Women who are pregnant or nursing;
• Had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to signing informed consent
• Have been treated with an investigational agent within 4 weeks prior to signing the informed consent form
• Have ongoing clinically significant adverse event(s) due to chemotherapy, radiotherapy or investigational agents administered more than 4 weeks prior to signing the informed consent as determined by the Investigator
• Have known or suspected hypersensitivity to azacitidine or mannitol
• Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Have low blood pressure (supine blood pressure <90/60 mmHg)
• Have human immunodeficiency virus (HIV), or active hepatitis virus B or C
• Have advanced malignant hepatic tumors
• Have end stage renal disease requiring dialysis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jay Backstrom, MD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

Sutter East Bay Hospitals

Berkeley, California, United States

Palm Springs Research Institute

Hialeah, Florida, United States

MCG Cancer Center

Augusta, Georgia, United States

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, United States

University of Kentucky-Markey Cancer Center Clinical Research Organization

Lexington, Kentucky, United States

Nevada Cancer Institute

Las Vegas, Nevada, United States

Montefiore Medical Center

The Bronx, New York, United States

Mid Dakota Clinical P.C. - Cancer Treatment and Research Center

Bismarck, North Dakota, United States

Gabrail Cancer Center

Canton, Ohio, United States

Pharma Resource

East Providence, Rhode Island, United States

Cancer Therapy and Research Center

San Antonio, Texas, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 30091166 (View on PubMed)

Platzbecker U, Middeke JM, Sockel K, Herbst R, Wolf D, Baldus CD, Oelschlagel U, Mutherig A, Fransecky L, Noppeney R, Bug G, Gotze KS, Kramer A, Bochtler T, Stelljes M, Groth C, Schubert A, Mende M, Stolzel F, Borkmann C, Kubasch AS, von Bonin M, Serve H, Hanel M, Duhrsen U, Schetelig J, Rollig C, Kramer M, Ehninger G, Bornhauser M, Thiede C. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018 Dec;19(12):1668-1679. doi: 10.1016/S1470-2045(18)30580-1. Epub 2018 Nov 12.

Reference Type: BACKGROUND

PMID: 30442503 (View on PubMed)

Stevens B, Winters A, Gutman JA, Fullerton A, Hemenway G, Schatz D, Miltgen N, Wei Q, Abbasi T, Vali S, Singh NK, Drusbosky L, Cogle CR, Hammes A, Abbott D, Jordan CT, Smith C, Pollyea DA. Sequential azacitidine and lenalidomide for patients with relapsed and refractory acute myeloid leukemia: Clinical results and predictive modeling using computational analysis. Leuk Res. 2019 Jun;81:43-49. doi: 10.1016/j.leukres.2019.04.005. Epub 2019 Apr 13.

Reference Type: BACKGROUND

PMID: 31009835 (View on PubMed)

Laille E, et al. A 2-Part Phase I Study in Patients with Solid or Hematologic Malignancies: Dose Proportionality of Subcutaneous (SC) Azacitidine (AZA) and Pharmacokinetics of SC AZA in Patients with Severe Renal Impairment . Presented at American Society of Hematology 2011, December 10-13, 2011, San Diego, CA. Abstract No. 3480.

Reference Type: BACKGROUND

Du X, Lai YY, Xiao Z, Liu T, Hu Y, Sun A, Li X, Shen ZX, Jin J, Yu L, Laille E, Dong Q, Songer S, Beach CL. Efficacy, safety and pharmacokinetics of subcutaneous azacitidine in Chinese patients with higher risk myelodysplastic syndromes: Results from a multicenter, single-arm, open-label phase 2 study. Asia Pac J Clin Oncol. 2018 Jun;14(3):270-278. doi: 10.1111/ajco.12835. Epub 2017 Dec 28.

Reference Type: BACKGROUND

PMID: 29282890 (View on PubMed)

Other Identifiers

AZA PH US 2007 PK006

Identifier Type: -

Identifier Source: org_study_id