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

NCT00379912 | Terminated Phase 2 Results DMC

• 1 other identifier: HOG MDS04-85
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

• Overall Response After Cycle 3

  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.

  3 months

• Overall Response Rate After Six Cycles

  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.

  6 months

Secondary Outcomes (6)

• Safety Profile of the Modified Dose/Schedule of Azacitidine and Erythropoietin or a Modified Dose of Azacitidine Alone

  24 months

• Duration of Significant Responses

  24 months

• Quality of Life

  24 months

• Analysis of CD34, CD71, CD36 Cells in Aspirated Bone Marrow for Both Responders and Non-responders at Baseline and After Three and Six Cycles

  6 months

• Percent Apoptosis in 34+36+71+ Cells at Baseline, Three Cycles and Six Cycles

  Six months

Study Arms (2)

Investigational Arm A

EXPERIMENTAL

Azacitidine + Erythropoietin

Drug: Azacitidine; Drug: Erythropoietin

Investigational Arm B

EXPERIMENTAL

Azacitidine

Drug: Azacitidine (Monotherapy)

Interventions

Azacitidine DRUG

Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.

Also known as: Vidaza

Investigational Arm A

Erythropoietin DRUG

Erythropoietin 60,000IU subcutaneous injection weekly while on protocol therapy

Also known as: EPO

Investigational Arm A

Azacitidine (Monotherapy) DRUG

Azacitidine 50 mg/m2 subcutaneously qod for two consecutive weeks every four weeks.

Also known as: Vidaza

Investigational Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Larry Cripe, MD: lead
• Celgene Corporation: collaborator
• Ortho Biotech Clinical Affairs, L.L.C.: collaborator
• Walther Cancer Institute: collaborator

Study Sites (9)

Medical & Surgical Specialists, LLC

Galesburg, Illinois, 61401, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Quality Cancer Center (MCGOP)

Indianapolis, Indiana, 46202, United States

Location

Arnett Cancer Care

Lafayette, Indiana, 47904, United States

Location

Horizon Oncology Center

Lafayette, Indiana, 47905, United States

Location

Medical Consultants, P.C.

Muncie, Indiana, 47303, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46601, United States

Location

Center for Hematology-Oncology of S Michigan

Jackson, Michigan, 49201, United States

Location

Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Related Publications (1)

• Sayar H, Chan RJ, Orschell CM, Chan EM, Yu Z, Hood D, Plett A, Yang Z, Hui CL, Nabinger SC, Kohlbacher KJ, West ES, Walter A, Sampson C, Wu J, Cripe LD. Thrice weekly azacitidine does not improve hematological responses in lower-risk myelodysplastic syndromes: a study of the Hoosier Oncology Group. Leuk Res. 2011 Aug;35(8):1108-10. doi: 10.1016/j.leukres.2011.02.025. Epub 2011 Mar 21.

  PMID: 21420732 RESULT

Related Links

• Hoosier Oncology Group Home Page

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine; Erythropoietin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Results of interim analysis led to early closure of the study.

Results Point of Contact

• Title: Clinical Data Coordinator
• Organization: Hoosier Cancer Research Network, Inc.

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Larry Cripe, M.D.

  Hoosier Oncology Group, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: September 21, 2006
• First Posted: September 25, 2006
• Study Start: September 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: February 14, 2018
• Results First Posted: May 31, 2017

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)