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Azacitidine and Erythropoietin Versus Azacitidine Alone for Patients With Low-Risk Myelodysplastic Syndromes

This study has been terminated.
(Insufficient response rate)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00379912
First Posted: September 25, 2006
Last Update Posted: May 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Celgene Corporation
Ortho Biotech Clinical Affairs, L.L.C.
Walther Cancer Institute
Information provided by (Responsible Party):
Larry Cripe, MD, Hoosier Cancer Research Network
  Purpose
This trial is designed to explore a modified dose and schedule of azacitidine in order to more effectively address the needs of patients with low-risk myelodysplastic syndromes (MDS), i.e., to alter the natural history of the disease without excessive toxicity or burden. The administration of erythropoietin is designed to influence the differentiation of primitive hematopoietic cells in which azacitidine has reversed the abnormal phenotype to red blood cells for patients in whom inadequate production of red blood cells is the major clinical issue.

Condition Intervention Phase
Myelodysplastic Syndromes Drug: Azacitidine Drug: Erythropoietin Drug: Azacitidine (Monotherapy) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial With A Modified Dose & Schedule of Subcutaneously Administered Azacitidine & Erythropoietin v Azacitidine Alone in Patients With Low-Risk Myelodysplastic Syndromes (Less Than 11% Marrow & Peripheral Blood Blasts)

Resource links provided by NLM:


Further study details as provided by Larry Cripe, MD, Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Overall Response After Cycle 3 [ Time Frame: 3 months ]

    Overall response for participants who have completed at least three cycles of protocol-specified therapy according to the International Working Group to Standardize Response Criteria for Myelodysplastic Syndromes criteria for Erythroid Response (HI-E) Major response: For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence.

    Minor response: For patients with pretreatment hemoglobin less than 11 g/dL, 1 to 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, 50% decrease in transfusion requirements.


  • Overall Response Rate After Six Cycles [ Time Frame: 6 months ]

    Overall response rate for participants who have completed at least six cycles of protocol-specified therapy according to the International Working Group to Standardize Response Criteria for Myelodysplastic Syndromes criteria for Erythroid Response (HI-E) Major response: For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence.

    Minor response: For patients with pretreatment hemoglobin less than 11 g/dL, 1 to 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, 50% decrease in transfusion requirements.



Secondary Outcome Measures:
  • Safety Profile of the Modified Dose/Schedule of Azacitidine and Erythropoietin or a Modified Dose of Azacitidine Alone [ Time Frame: 24 months ]
    Full adverse event information is submitted in the record below. A summary of the Significant Toxicities Rate (clinically significant myelosuppression (CTCAE Grade 3 or 4 neutropenia or thrombocytopenia)) over all patients receiving at least 1 dose of study medication at the time of interim analysis is reported in this outcome measure.

  • Duration of Significant Responses [ Time Frame: 24 months ]
    Data for this outcome measure was not collected or analyzed due to the termination of the study.

  • Quality of Life [ Time Frame: 24 months ]
    Data for this outcome measure was not collected or analyzed due to the termination of the study

  • Analysis of CD34, CD71, CD36 Cells in Aspirated Bone Marrow for Both Responders and Non-responders at Baseline and After Three and Six Cycles [ Time Frame: 6 months ]
  • Percent Apoptosis in 34+36+71+ Cells at Baseline, Three Cycles and Six Cycles [ Time Frame: Six months ]
  • BclXL Expression [ Time Frame: Six months ]

Enrollment: 15
Study Start Date: September 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Investigational Arm A
Azacitidine + Erythropoietin
Drug: Azacitidine
Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Other Name: Vidaza
Drug: Erythropoietin
Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy
Other Name: EPO
Experimental: Investigational Arm B
Azacitidine
Drug: Azacitidine (Monotherapy)
Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.
Other Name: Vidaza

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A bone marrow (BM) aspirate and biopsy that demonstrates MDS with less than 11% blasts.
  • Conventional metaphase cytogenetics done within 90 days prior to registration for screening.
  • Central pathology review, correlative submission and confirmation of diagnosis is required prior to initiation of therapy (see Study Procedure Manual for details of submission). The FAB and WHO classification of MDS and the IPSS score will be determined at time of central pathology review.
  • Correlative marrow aspirate obtained.

To be eligible for randomization, subjects must have documentation of at least 1 of the following:

  • A transfusion dependent anemia (defined by a history of two or more episodes of transfusion within a period of 8 weeks).
  • An untransfused hemoglobin < 10 gm/dl measured on at least two occasions more than 7 days apart in the month prior to randomization.

Patients must also meet 1 of the following criteria:

  • Has not received prior erythropoietin and has a serum erythropoietin level > 200 IU/L within 14 days of randomization.
  • Has received prior erythropoietin without clinical benefit in the judgment of the treating physician.
  • Adequate iron status defined as serum ferritin > 20 ng/ml and transferrin saturation of > 30% within 90 days prior to randomization.
  • Symptoms attributed to the anemia with hemoglobin < 11 g/dL.
  • Folate and Vitamin B12 levels within normal limits within 90 days prior to randomization.
  • Life expectancy > 6 months as judged by the treating investigator.

Exclusion Criteria:

  • No known history of intolerance to erythropoietic agents.
  • No prior intensive cytotoxic chemotherapy for a myeloid malignancy including MDS.
  • Patients with a history of a non-myeloid malignancy with secondary MDS are eligible for study enrollment provided, in the opinion of the treating investigator and the study chair, the anticipated behavior of the non-myeloid malignancy will not interfere with study participation and evaluation of outcome.
  • No known or suspected hypersensitivity to azacitidine or mannitol.
  • No hepatic tumors.
  • No uncontrolled hypertension (defined as a systolic pressure > 160 mmHg and/or a diastolic pressure > 110 mmHg).
  • No known hypersensitivity to mammalian cell-derived products or human albumin.
  • No history of (within 12 months) deep venous thrombosis (DVT), pulmonary embolism (PE), or other venous thrombosis. Prior superficial thrombophlebitis is not an exclusion criterion.
  • No history of (within 6 months) cerebrovascular accident ([CVA] includes ischemic, embolic and hemorrhagic), transient ischemic attack (TIA), myocardial ischemia (includes Unstable Angina, Q wave Myocardial Infarction [QwMI] and non-Q wave Myocardial Infarction [NQMI], or other arterial thrombosis.
  • Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 4-week period thereafter.
  • Females with childbearing potential must have a negative pregnancy test within 7 days prior to being randomized. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00379912


Locations
United States, Illinois
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Quality Cancer Center (MCGOP)
Indianapolis, Indiana, United States, 46202
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
United States, Michigan
Center for Hematology-Oncology of S Michigan
Jackson, Michigan, United States, 49201
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
Sponsors and Collaborators
Larry Cripe, MD
Celgene Corporation
Ortho Biotech Clinical Affairs, L.L.C.
Walther Cancer Institute
Investigators
Study Chair: Larry Cripe, M.D. Hoosier Oncology Group, LLC
  More Information

Additional Information:
Publications:
Responsible Party: Larry Cripe, MD, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00379912     History of Changes
Other Study ID Numbers: HOG MDS04-85
First Submitted: September 21, 2006
First Posted: September 25, 2006
Results First Submitted: February 9, 2017
Results First Posted: May 31, 2017
Last Update Posted: May 31, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Epoetin Alfa
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Hematinics