LeukemiaPhase 2NCT00997243
Azacitidine and Lintuzumab in Treating Patients With Previously Untreated Myelodysplastic Syndromes
A Phase 2 study testing lintuzumab and 5-azacytidine in people with Leukemia and Myelodysplastic Syndromes, run by Alison Walker at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- lintuzumab and 5-azacytidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to May 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: Phase II Study of 5-azacytidine and Lintuzumab in Myelodysplastic Syndromes (MDS)
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.
Read the detailed description
OBJECTIVES:
Primary
- To determine the complete response rate of the combination of lintuzumab and azacitidine in patients with myelodysplastic syndromes.
Secondary
- 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 response.
- 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.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- lintuzumab, 5-azacytidine
- 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
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Anemia, Refractory, with Excess of Blasts, Anemia, Refractory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lintuzumabBiological
Also called SGN-33
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.
5-azacytidineDrug
Also called Vidaza, AZA
75mg/m2 IV/SC daily on days 1-7.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: lintuzumab; Drug: 5-azacytidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 5 years
Secondary outcomes (6)
Overall 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.
Measured: up to 5 years
Toxicities of the Combination
All patients who received study drug were closely monitored for adverse events (AEs). All AEs that occured during study period were reported and the investigator determined the severity and relationship to study drug (unrelated, unlikely, possibly, probably, or definitely related). The NCI's CTCAE(Common Toxicity Criteria for Adverse Effects)v3.0 was used for grading AEs.
Measured: 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
Measured: 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)
Measured: up to 5 years
Perform Exploratory Studies of AZA-triphosphate With Global DNA Methylation
Measured: up to 5 years
Explore the Biologic Role of microRNAs in Determining Clinical Response to the AZA Plus Lintuzumab Combination and Achievement of the Other Pharmacodynamic Endpoints
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2009 (estimated)
- Study startNov 2009
- Primary completionSep 2010
- Study completionMay 2011
Why it stopped: Drug no longer being supplied by sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alison Walker
- Sponsor type
- University, hospital or other
- Collaborators
- Seagen Inc.
- Responsible party
- Sponsor-investigator, Alison Walker, Ohio State University Comprehensive Cancer Center
- Investigators
- Alison Walker, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00997243
- Sponsor's protocol ID
- OSU-09034
- Other IDs
- NCI-2011-03159
- Status last verified
- Apr 2017
- First submitted
- 16 Oct 2009
- Last updated
- 10 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of 5-azacytidine and Lintuzumab in Myelodysplastic Syndromes (MDS)
- ClinicalTrials.gov ID
- NCT00997243
- Acronym / sponsor ID
- OSU-09034
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug no longer being supplied by sponsor
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Alison WalkerUniversity, hospital or other
- Collaborators
- Seagen Inc.
- Study start
- Nov 2009 (actual)
- Primary completion
- Sep 2010 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 19 Oct 2009 (estimated)
- Results
- Posted 26 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To determine the complete response rate of the combination of lintuzumab and azacitidine in patients with myelodysplastic syndromes.
Secondary
- 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 response.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-azacytidine and Lintuzumab | Experimental | Biological: lintuzumab, Drug: 5-azacytidineCycle 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lintuzumabAlso: SGN-33Cycle 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. | Biological | 5-azacytidine and Lintuzumab |
| 5-azacytidineAlso: Vidaza, AZA75mg/m2 IV/SC daily on days 1-7. | Drug | 5-azacytidine and Lintuzumab |
Primary outcome
Complete Response Rate
Time frame: up to 5 years
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.
6 secondary outcomes
Overall Response Rate
Time frame: up to 5 years
Toxicities of the Combination
Time frame: 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
Time frame: 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)
Time frame: up to 5 years
Perform Exploratory Studies of AZA-triphosphate With Global DNA Methylation
Time frame: up to 5 years
Explore the Biologic Role of microRNAs in Determining Clinical Response to the AZA Plus Lintuzumab Combination and Achievement of the Other Pharmacodynamic Endpoints
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- JameslineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Walker, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lintuzumab and 5-azacytidine in people with Leukemia and Myelodysplastic Syndromes, run by Alison Walker at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Response Rate (time frame: up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2017.