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Study Summary
No. 2012-0866:.......Leukemia......Farhad Ravandi-Kashani......Leukemia
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Study Summary Title
Study Summary
Number:
2012-0866
Study Title:A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO COMPARE EFFICACY AND SAFETY OF ORAL AZACITIDINE PLUS BEST SUPPORTIVE CARE VERSUS BEST SUPPORTIVE CARE AS MAINTENANCE THERAPY IN SUBJECTS WITH ACUTE MYLOID LEUKEMIA IN COMPLETE REMISSION
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Physician New Patient Referral
Name:Farhad Ravandi-KashaniPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-745-0394
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:Celgene
Phase of Study:Phase IIIReturn
Visit:
Treatment
Agents:
AzacitidineHome Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to learn taking oral azacitidine
can help keep the disease from returning. In this study, azacitidine will be
compared with a placebo. The safety and tolerability of oral azacitidine will
also be studied.

Azacitidine is designed to block certain proteins in cancer cells whose job is
to stop the function of the tumor-fighting proteins. By blocking the "bad"
proteins, the tumor-fighting genes may be able to work better.

A placebo is not a drug. It looks like the study drug but is not designed to
treat any disease or illness. It is designed to be compared with a study drug
to learn if the study drug has any real effect.
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Study Objectives / Outcomes
Primary Objective
The primary objective of the study is to demonstrate if maintenance therapy with oral azacitidine improves overall survival (OS) compared with placebo in subjects with acute myeloid leukemia (AML), age >/=55 years, who have achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after induction with intensive chemotherapy with or without consolidation chemotherapy.

Secondary Objectives
The secondary objectives of the study are:
  • To determine relapse-free-survival (RFS);
  • To determine safety, tolerability; and
  • To determine the effect of oral azacitidine compared with placebo on health-related quality of life (HRQoL) and healthcare resource utilization.

Exploratory Objectives
The exploratory objectives of the study are:
  • To determine complete cytogenetic remission (CRc) rate;
  • To evaluate molecular and/or cellular markers in the bone marrow post-induction and during maintenance therapy that may be predictive of clinical outcomes with therapy (placebo or oral azacitidine), including OS and RFS, following CR/CRi; and
  • To evaluate exploratory HRQoL measures.

Data from exploratory objectives may not be included in the Clinical Study Report.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:03/05/2013
Study Type:Phase Iii
Recruitment Status:Open
Projected Accrual:460
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male or female subjects >/=55 years of age at the time of signing the ICD

2) Newly diagnosed, histologically confirmed de novo AML or AML secondary to prior myelodysplastic disease

3) Should have undergone induction therapy with intensive chemotherapy with or without consolidation therapy

4) Should have achieved first CR/CRi status within 3 months prior to randomization, as evidenced by the following: Complete Remission (CR) -- < 5% blasts in bone marrow, absence of blasts with Auer rods, absence of extramedullary disease, independence on blood transfusions, peripheral neutrophil count > 1.0 x 10^9/L, platelet count >/=100 x 109/L; or Complete Remission with Incomplete Blood Count Recovery (CRi) -- < 5% blasts in bone marrow, absence of blasts with Auer rods, absence of extramedullary disease, independence on blood transfusions, peripheral neutrophil count < 1.0 x 10^9/L or platelet count < 100 x 10^9/L.

5) ECOG performance status of 0, 1, 2 or 3

6) Adequate bone marrow function based on ANCs >/= 0.5 x 10^9/L and platelet counts >/= 20,000 x 10^9/L

7) Adequate organ function, defined as: Serum bilirubin </=1.5 times the upper limit of normal (ULN); Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </=2.5 times the ULN; Serum creatinine </=2.5 times the ULN

8) Females of child bearing potential (FCBP)* may participate, providing they meet the following conditions: Agree to practice abstinence; or Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months following the last dose of oral azacitidine; and Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at screening; and Have a negative serum or urine pregnancy test (Investigator's discretion) within 72 hours prior to starting study therapy in the double-blind treatment phase (note that the screening serum pregnancy test can be used as the test prior to starting study therapy in the double-blind treatment phase if it is performed within the 72-hour timeframe).

9) Male subjects with a female partner of childbearing potential must agree to practice abstinence or to the use of a physician-approved contraceptive method throughout the course of the study and avoid fathering a child during the course of the study and for 3 months following the last dose of azacitidine

10) Understand and voluntarily sign an ICD prior to any study related assessments/procedures are conducted

11) Able to adhere to the study visit schedule and other protocol requirements

12) Ability to swallow study medication

Exclusion Criteria:1) Suspected or proven acute promyelocytic leukemia (FAB M3) based on morphology, immunophenotype, molecular assay, or karyotype; or AML with previous hematologic disorder such as chronic myeloid leukemia or myeloproliferative neoplasms, excluding MDS

2) AML associated with inv(16), t(8;21), t(16;16), t(15;17), or t(9;22) karyotypes or molecular evidence of such translocations

3) Prior bone marrow or stem cell transplantation

4) Have achieved CR/CRi following therapy with hypomethylating agents

5) Received therapy with hypomethylating agents for MDS and went on to develop AML within four months of discontinuing the therapy with hypomethylating agents

6) Proven central nervous system leukemia

7) Candidate for allogeneic bone marrow or stem cell transplant at screening

8) Diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure)

9) Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure

10) Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)

11) Known active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B (HBV) or C (HCV)

12) Known or suspected hypersensitivity to azacitidine or mannitol

13) Use of any other experimental drug or therapy within 28 days prior to Day 1 of Cycle 1

14) Unwilling or unable to complete patient reported outcome assessments without assistance or with minimal assistance from trained site personnel and/or caregiver

15) Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

16) Any significant medical condition, laboratory abnormality, or psychiatric illness that would interfere or prevent the subject from participating in the study

17) Any condition that confounds the ability to interpret data from the study

18) Any condition causing an inability to swallow tablets

19) Any condition that would impair absorption of the study medication (i.e. short gut, malabsorption syndrome)

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Links
Registration Number: NCT01757535
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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