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A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes

Primary Purpose

Myelodysplastic Syndromes

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Azacitidine

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring MDS either de novo or secondary, fitting any of the WHO classifications.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Pathological MDS either de novo or secondary, fitting any of the FAB classifications, confirmed by institutional pathologist within 2 weeks prior to start of treatment. Patients with 5% bone marrow blasts must also meet one of the following criteria:
- Symptomatic anemia with either hemoglobin less than 10.0 g/dL or requiring RBC transfusion
- Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or
- Neutropenia with two or more absolute neutrophil counts less than 1,000 /µL.
ECOG performance status of 0-2.
Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.
Adequate renal and hepatic function (creatinine ≤ 150% of institutional upper limit of normal, total bilirubin ≤ 150% institutional upper limit of normal, AST ≤ 200% institutional upper limit of normal).
Life expectancy of at least 12 weeks.
Have not received any chemotherapy within 4 weeks of study enrollment and must have recovered from any treatment-related toxicities.
Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy.
Sexually active women of childbearing potential must use effective birth control during the trial and for an appropriate period after the trial.
Men must be willing to avoid fathering a new child while receiving therapy with azacitidine.
≥18 years, no upper age limit
Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous azacitidine alone as a treatment prior to transplantation.

Exclusion Criteria:

Known CNS leukemia.
Previously received Azacitidine (Vidaza®, Pharmion Corp., Boulder CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).
Known or suspected hypersensitivity to azacitidine or mannitol.
Receiving any other investigational agents within 30 days of first dose of study drug.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
Known positive serology for HIV.
Had radiotherapy within 14 days prior to study enrollment.
Known presence of hepatic tumors.
<18 years of age
Exclude women who are pregnant or breast feeding.

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Azacitidine

Arm Description

Azacitidine 75 mg/m2 IV on days 1-5 of each 28 day cycle. Patients that do not respond after two cycles will have the dose increased to 100 mg/m2. Patients who achieve a CR will receive 3 additional 28 day cycles and then begin treatment on days 1-5 of a 56 day cycle. Individuals who demonstrate a loss of response will resume 28 day cycles.

Outcomes

Primary Outcome Measures

Rate of Complete Remission (CR) and Partial Remission (PR)

Defined according to the modified International Working Group (IWG) (2006) response criteria for myelodysplasia: CR=bone marrow with <5% myeloblasts and 0% peripheral blasts, hemoglobin ≥11g/dL, platelets ≥ 100 x 10^9/L, and neutrophils ≥1.0 x 10^9/L. Residual dysplasia was allowed. PR= All of the CR criteria if abnormal before treatment except: bone marrow blasts decreased by ≥50% over pretreatment but still >5%.

Secondary Outcome Measures

Rate of Hematologic Improvement

International Working Group (IWG) for Myelodysplasia (MDS).

Rate of Transfusion Independence

Rate of Cytogenetic Response

Rate of Overall Survival

Overall survival is defined as the date of first dose of study drug to the date of death from any cause.

Rate of Relapse After Hematopoietic Stem Cell Transplant in Individuals Treated With 5-azacitidine Prior to Transplant.

Full Information

NCT ID

NCT00384956

First Posted

October 4, 2006

Last Updated

October 27, 2016

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT00384956

Brief Title

A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes

Official Title

A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Completed

Study Start Date

August 2006 (undefined)

Primary Completion Date

August 2008 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary endpoint of this study is to estimate morphologic complete remission rate. Estimation of response rate is also a secondary objection.

Detailed Description

Myelodysplastic syndrome (MDS) is a hematological disorder characterized by ineffective hematopoiesis. The only known curative treatment for patients with MDS is allogeneic stem cell transplantation. However, only a minority of patients are candidates for this aggressive therapy. DNA hypomethylation agents have been shown to have activity in this disorder and are postulated to work by reversing this epigenetic mechanism of gene-silencing. Recently, 5-azacitidine, administered subcutaneously for seven days, received approval by the FDA for the therapy of MDS based on a randomized trial which demonstrated a diminished risk of leukemic transformation and improved survival when compared to best supportive care. The subcutaneous route of administration can present challenges to implementing this therapy. In the CALGB studies 8921 and 9221, approximately 23% of patients had significant injection site pain. Moreover, 35 % of patients had injection site bruising which can be extensive in thrombocytopenic patients. Due to limitations on drug concentration and administration volumes for subcutaneous dosing, patients often need to have two or three injections at separate sites each day to meet target dosing. In addition, the schedule of administration is inconvenient in an outpatient setting secondary to the need to schedule administrations over weekends. Therefore, there is great interest in pursuing an abbreviated intravenous route for administration of the drug.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndromes

Keywords

MDS either de novo or secondary, fitting any of the WHO classifications.

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Azacitidine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Other Intervention Name(s)

5-azacitidine, Vidaza

Primary Outcome Measure Information:

Title

Rate of Complete Remission (CR) and Partial Remission (PR)

Description

Time Frame

After 4 cycles of therapy (up to 112 days after start of treatment)

Secondary Outcome Measure Information:

Title

Rate of Hematologic Improvement

Description

International Working Group (IWG) for Myelodysplasia (MDS).

Time Frame

4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]

Title

Rate of Transfusion Independence

Time Frame

4 weeks following last azacitidine dose [median number of cycles 4.5 (1-20)]

Title

Rate of Cytogenetic Response

Time Frame

2 years after first dose of study drug or until participant is lost to follow-up or dies

Title

Rate of Overall Survival

Description

Overall survival is defined as the date of first dose of study drug to the date of death from any cause.

Time Frame

2 years after first dose of study drug or until participant is lost to follow-up or dies

Title

Rate of Relapse After Hematopoietic Stem Cell Transplant in Individuals Treated With 5-azacitidine Prior to Transplant.

Time Frame

2 years after first dose of study drug or until participant is lost to follow-up or dies

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Pathological MDS either de novo or secondary, fitting any of the FAB classifications, confirmed by institutional pathologist within 2 weeks prior to start of treatment. Patients with 5% bone marrow blasts must also meet one of the following criteria: Symptomatic anemia with either hemoglobin less than 10.0 g/dL or requiring RBC transfusion Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or Neutropenia with two or more absolute neutrophil counts less than 1,000 /µL. ECOG performance status of 0-2. Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards. Adequate renal and hepatic function (creatinine ≤ 150% of institutional upper limit of normal, total bilirubin ≤ 150% institutional upper limit of normal, AST ≤ 200% institutional upper limit of normal). Life expectancy of at least 12 weeks. Have not received any chemotherapy within 4 weeks of study enrollment and must have recovered from any treatment-related toxicities. Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy. Sexually active women of childbearing potential must use effective birth control during the trial and for an appropriate period after the trial. Men must be willing to avoid fathering a new child while receiving therapy with azacitidine. ≥18 years, no upper age limit Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous azacitidine alone as a treatment prior to transplantation. Exclusion Criteria: Known CNS leukemia. Previously received Azacitidine (Vidaza®, Pharmion Corp., Boulder CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN). Known or suspected hypersensitivity to azacitidine or mannitol. Receiving any other investigational agents within 30 days of first dose of study drug. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements. Known positive serology for HIV. Had radiotherapy within 14 days prior to study enrollment. Known presence of hepatic tumors. <18 years of age Exclude women who are pregnant or breast feeding.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ravi Vij, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.siteman.wustl.edu

Description

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes

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