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Phase II Study of 5-azacytidine and Lintuzumab in Myelodysplastic Syndromes (MDS)

Phase 2
18 Years
Not Enrolling
Leukemia, Myelodysplastic Syndromes

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Trial Information

Phase II Study of 5-azacytidine and Lintuzumab in Myelodysplastic Syndromes (MDS)



- To determine the complete response rate of the combination of lintuzumab and
azacitidine in patients with myelodysplastic syndromes.


- To define the specific toxicities of this regimen.

- To determine the overall response rate.

- To determine the relationship between pretreatment expression of Syk and clinical

- To determine whether the investigational agents modulate Syk expression and to
correlate drug-induced changes in Syk with response to treatment.

- To provide preliminary data on the biological activity of azacitidine as a
demethylating agent (changes in target gene methylation and gene expression, DNMT1
protein expression, global methylation).

- To perform exploratory studies of azacitidine-triphosphate with global DNA methylation.

- To explore the biologic role of microRNA in determining clinical response to this
regimen and achievement of the other pharmacodynamic endpoints.

OUTLINE: Patients receive azacitidine IV or subcutaneously once daily on days 1-7 and
lintuzumab IV on days 2, 7, 15, and 22 (days 2 and 15 of course 1 only). Treatment repeats
every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Treatment modifications may apply according to response.

Blood and bone marrow samples are collected periodically for pharmacodynamic studies.

After completion of study treatment, patients are followed up for 5 years.

Inclusion Criteria

Eligibility Criteria:

- Age >18 with untreated MDS by FAB or WHO criteria (note: FAB criteria for MDS
includes <29% blasts; FAB criteria includes CMML).

- Patients with therapy related disease (t-MDS).

- If the patient has co-morbid medical illness, life expectancy attributed to this must
be greater than 6 months.

- Eastern Cooperative Oncology Group (ECOG) performance status <2.

- Must have adequate organ function as defined below:

- total bilirubin <2.0mg/dL

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

- creatinine <2.0mg/dL

- NYHA CHF Class II or better

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence).

- Ability to understand and willingness to sign the written informed consent document.

- CD33 expression is required on at least 25% of left shifted dysplastic myeloid cells,
including blasts. This testing will be done on bone marrow aspirate, but for patients
whose CD33 expression in this cellular compartment cannot be ascertained, peripheral
blood will be allowed to determine this.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 6 months (for other
cancers) prior to entering the study.

- Patients receiving any other investigational agents or patients that have received
other investigational agents within 1 month of enrollment.

- Patients with active central nervous system disease or with granulocytic sarcoma as
sole site of disease.

- Patients with history of allergic reactions attributed to compounds of similar
chemical or biologic composition to AZA or lintuzumab that are not easily managed are
excluded. Patients with hypersensitivity to mannitol are excluded.

- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements. As infection is a common feature of MDS, patients with active infection
are permitted to enroll provided that the infection is under control. Myocardial
infarction within 6 months prior to enrollment or has New York Heart Association
(NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active
conduction system abnormalities.

- Psychiatric conditions that prevent compliance with protocol or consent.

- Pregnant women or women who are breastfeeding are excluded from this study.

- HIV-positive patients on combination antiretroviral therapy are ineligible.

- Patients with serious medical or psychiatric illness likely to interfere with
participation in this clinical study.

- Patients with serious medical or psychiatric illness likely to interfere with
participation in this clinical study.

- Patients with baseline fibrinogen <100mg/dL, or those with clinically significant
disseminated intravascular coagulation, are excluded.

- Patients who require ongoing therapeutic anticoagulation with warfarin, lovenox, or
similar agent are excluded. This does not apply to patients on low dose prophylaxis

- Patients who require ongoing clopidogrel therapy are excluded. In cases where
clopidogrel use at screening is subsequently discontinued due to ongoing or future
risk of drug and treatment related cytopenias, such patients will be eligible.

- Patients with platelet <10,000/uL who are refractory to platelet transfusion are not
eligible (must bump to at least >10,000/uL after transfusion)

- Patients who have previously received lenalidomide or thalidomide are excluded.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete response rate

Outcome Time Frame:

up to 5 years

Safety Issue:


Principal Investigator

Alison Walker, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2009

Completion Date:

May 2011

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • de novo myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • chronic myelomonocytic leukemia
  • refractory anemia with excess blasts in transformation
  • refractory anemia with excess blasts
  • refractory anemia with ringed sideroblasts
  • refractory anemia
  • refractory cytopenia with multilineage dysplasia
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia



Ohio State University Medical CenterColumbus, Ohio  43210