Azacitidine and Lintuzumab in Treating Patients With Previously Untreated Myelodysplastic Syndromes

NCT00997243 | Terminated Phase 2 Results DMC

• 2 other identifiers: OSU-09034NCI-2011-03159
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as lintuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving chemotherapy together with monoclonal antibodies may be a better way to block cancer growth. PURPOSE: This phase II trial is studying the side effects and how well giving azacitidine together with lintuzumab works in treating patients with previously untreated myelodysplastic syndromes.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  Response to therapy was determined based on percentage of blasts in bone marrow, hematopoiesis, and requirement for supportive care (i.e., transfusions or cytokine growth factors). The modified International Working Group response criteria was used, based on Cheson, et al.

  up to 5 years

Secondary Outcomes (6)

• Overall Response Rate

  up to 5 years

• Toxicities of the Combination

  up to 5 years

• Determine the Relationship Between Pretreatment Expression of Syk and Clinical Response; to Determine Whether the Investigational Agents Modulate Syk Expression and Correlate Drug-induced Changes in Syk With Response to Treatment

  up to 5 years

• Provide Preliminary Data on the Biological Activity of AZA as a Demethylating Agent (Changes in Target Gene Methylation and Gene Expression, DNMT1[Deoxyribonucleic Acid Methyltransferase 1 DNA Methyltransferase 1]Protein Expression, Global Methylation)

  up to 5 years

• Perform Exploratory Studies of AZA-triphosphate With Global DNA Methylation

  up to 5 years

Study Arms (1)

5-azacytidine and Lintuzumab

EXPERIMENTAL

Cycle 1- 5-azacytidine (Vidaza, AZA) 75mg/m2 IV/SC(subcutaneous)daily on days 1-7. Subsequent Cycles (cycles to be repeated every 28 days) AZA 75mg/m2 IV/SC daily on days 1-7.

Biological: lintuzumab; Drug: 5-azacytidine

Interventions

lintuzumab BIOLOGICAL

Cycle 1 600mg as an IV infusion (flat dose for all), given on days 2, 7, 15, and 22. Subsequent Cycles (cycles to be repeated every 28 days) 600mg as an IV infusion, given every other week, twice during each cycle, including one dose given during AZA therapy. Doses should be given at least 12 days apart. By convention, dosing on days 7 and 22 of each cycle will be encouraged, but due to expected issues of patient convenience (time, travel, etc.), the study requirements are every other week, twice during each cycle, with one dose during AZA treatment.

Also known as: SGN-33

5-azacytidine and Lintuzumab

5-azacytidine DRUG

75mg/m2 IV/SC daily on days 1-7.

Also known as: Vidaza, AZA

5-azacytidine and Lintuzumab

Eligibility Criteria

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

You may not qualify if:

• 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 therapy.
• 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.

Sponsors & Collaborators

• Alison Walker: lead
• Seagen Inc.: collaborator

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Jamesline

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory

Interventions

lintuzumab; Azacitidine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

The study was terminated early by the sponsor due to the removal of lintuzumab from the market.

Results Point of Contact

• Title: Alison Walker, MD
• Organization: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Alison.Walker@osumc.edu

614-293-3196

Study Officials

• Alison Walker, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 16, 2009
• First Posted: October 19, 2009
• Study Start: November 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: May 1, 2011
• Last Updated: May 10, 2017
• Results First Posted: November 26, 2013

Record last verified: 2017-04

Locations

US (1)