LeukemiaPhase 2NCT00398047
Azacitidine, Darbepoetin Alfa, and Erythropoietin and Filgastrim (G-CSF) in Treating Patients With Myelodysplastic Syndromes
A Phase 2 study testing Azacitadine and Hematopoietic Growth Factors in people with Leukemia and Myelodysplastic Syndromes, run by Wake Forest University Health Sciences 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 abnormal cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages Up to 120 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Azacitadine and Hematopoietic Growth Factors
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2006to Sep 2009
- 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 Up to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of myelodysplastic syndromes (MDS)
- Bone marrow aspirate and biopsy with karyotyping performed within the past 8 weeks
- Patients with chronic myelomonocytic leukemia (CMML), refractory anemia (RA), or refractory anemia with ringed sideroblasts (RARS) according to FAB classification OR RA, RARS, refractory anemia with multilineage dysplasia, or RARS with multilineage dysplasia according to WHO classification must meet ≥ 1 of the following criteria:
- Symptomatic anemia requiring RBC transfusion for ≥ 3 months before study entry
- Thrombocytopenia with ≥ 2 platelet counts < 50,000/mm³ OR a significant hemorrhage requiring platelet transfusion
- Neutropenia with an absolute neutrophil count < 1,000/mm³ and an infection requiring IV antibiotics
- No refractory anemia with excess blasts in transformation
- No history of leukemia
- No known primary or metastatic hepatic tumor
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 2 months
- AST and ALT ≤ 2 times upper limit of normal
- Creatinine < 2.0 mg/dL
- Serum vitamin B12 normal
- Serum and/or red cell folate levels normal
- Ferritin ≥ 50 ng/mL
- Copper > 40 µg/dL
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
- No prior azacitidine or decitabine
- No prior therapy for MDS
- Supportive therapy within the past 28 days allowed
- No other concurrent treatment for MDS (i.e., thalidomide, arsenic trioxide, cyclosporine, or melphalan)
- No other concurrent hematopoietic growth factors, including epoetin alfa, filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11 (oprelvekin)
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
About this study
Official title: Combination of Azacitadine and Hematopoietic Growth Factors for Myelodysplastic Syndrome
RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as darbepoetin alfa and G-CSF, may increase the number of red blood cells and white blood cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving azacitidine together with darbepoetin alfa and G-CSF may be an effective treatment for myelodysplastic syndromes.
PURPOSE: This clinical trial is studying how well giving azacitidine together with darbepoetin alfa and G-CSF works in treating patients with myelodysplastic syndromes.
Read the detailed description
OBJECTIVES:
Primary
- Determine the hematological response rate in patients with myelodysplastic syndromes treated with azacitidine, darbepoetin alfa, and filgrastim (G-CSF).
Secondary
- Determine the time to leukemia progression, survival, and changes in apoptotic index of bone marrow in patients treated with this regimen.
OUTLINE: This is an open-label, nonrandomized study.
- Initial therapy (courses 1 and 2): Patients receive azacitidine subcutaneously (SC) or intra-venous (IV) on days 1-5 (week 1) and darbepoetin alfa* SC on day 8 (week 2). Treatment repeats every 28 days for 2 courses.
Patients undergo bone marrow aspirate and biopsy to assess response. Patients with a major hematological improvement OR with grade 3-4 hematological toxicities during the first 2 courses of therapy AND/OR ≥ 50% reduction in bone marrow cellularity compared to baseline proceed to optimization therapy A. Patients not meeting any of the above criteria proceed to optimization therapy B. Patients with disease progression are removed from study.
- Optimization therapy A (courses 3-8): Patients receive azacitidine SC or IV on days 1-5 (week 1), darbepoetin alfa** SC on day 8 (week 2), and filgrastim (G-CSF) SC 3 times weekly in weeks 2-4.
- Optimization therapy B (courses 3-8): Patients receive a higher dose of azacitidine on days 1-5 (week 1), darbepoetin alfa** SC on day 8 (week 2), and G-CSF 3 times weekly in weeks 2-4.
In both optimization therapy A and B, treatment repeats every 28 days for 6 courses. Patients with any degree of hematological improvement after initial therapy and optimization therapy proceed to maintenance therapy.
- Maintenance therapy (course 9 and all subsequent courses): Patients receive azacitidine on days 1-5 (week 1). Only patients with anemia (hemoglobin < 12 g/dL) and/or neutropenia (absolute neutrophil count < 1,500/mm ³) at the start of any given course during maintenance therapy receive darbepoetin alfa** SC beginning on day 8 (week 2) and continuing once every 21 days and G-CSF SC 3 times weekly beginning in week 2.
Courses repeat every 28-56 days (determined by the treating physician) in the absence of disease progression or unacceptable toxicity.
Bone marrow samples are obtained at baseline and after the completion of course 2 of study treatment for apoptosis analysis, flow cytometry, and gene expression profiles of p53 and p21 by immunohistochemistry. Peripheral blood samples are obtained periodically and analyzed for hemoglobin F quantitation.
NOTE: *Administered only if the patient is anemic (hemoglobin < 12 g/dL).
NOTE: **Darbepoetin alfa is held if hemoglobin > 12 g/dL on day 1 of a given cycle.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- Azacitadine and Hematopoietic Growth Factors
- Keywords
- de novo myelodysplastic syndromes, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia, refractory cytopenia with multilineage dysplasia, chronic myelomonocytic leukemia, secondary myelodysplastic syndromes, childhood myelodysplastic syndromes
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Anemia, Refractory, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azacitadine and Hematopoietic Growth FactorsDrug
Combination of Azacitadine and Hematopoietic Growth Factors
| Study group | Role | What they receive |
|---|---|---|
| Azacitadine and Hematopoietic Growth Factors | Experimental | Combination of Azacitadine andHematopoietic Growth Factors Receives: Drug: Azacitadine and Hematopoietic Growth Factors |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response
Complete response is normalization of abnormal blood counts, and disappearance of signs of morphological changes in the bone marrow. If the previously present cytogenetic abnormalities are absent then it is referred also as a cytogenetic complete remission.
Measured: Approximately 112 days
Rate of Major Hematological Improvement
For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for red cell transfusion-dependent patients, transfusion independence.
Measured: Approximately 112 days
Secondary outcomes (5)
Minor Hematological Improvements
For patients with pretreatment platelet count less than 100,000/mm3, a 50% or more increase in platelet count with a net increase greater than 10,000/mm3 but less than 30,000/mm3
Measured: Approximately 112 days
Time to Progression to Acute Myeloid Leukemia (Blast ≥ 20%) or Death
Death during treatment or disease progression characterized by worsening of cytopenias, increase in the percentage of the blasts, reduction of hemoglobin concentration by at least 2 g/dl or transfusion dependence in the absence of another explanation, such as acute infection, gastrointestinal bleeding, hemolysis.
Measured: Approximately 12 months
Overall Survival
Measured: Approximately 12 months
Change in Bone Marrow Apoptosis
Measured: Baseline and approximately 12 months
Expression of p53 and p21
Measured: Approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2006 (estimated)
- Study startSep 2006
- Primary completionSep 2009
- Study completionSep 2009
Why it stopped: Slow accrual
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.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- 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
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Bayard L. Powell, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00398047
- Sponsor's protocol ID
- CDR0000515108
- Other IDs
- P30CA012197, CCCWFU-29106
- Status last verified
- Aug 2018
- First submitted
- 9 Nov 2006
- Last updated
- 6 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Azacitadine and Hematopoietic Growth Factors for Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00398047
- Acronym / sponsor ID
- CDR0000515108
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Keywords
- de novo myelodysplastic syndromes, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia, refractory cytopenia with multilineage dysplasia, chronic myelomonocytic leukemia, secondary myelodysplastic syndromes, childhood myelodysplastic syndromes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 10 Nov 2006 (estimated)
- Results
- Posted 17 Apr 2012
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 abnormal cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as darbepoetin alfa and G-CSF, may increase the number of red blood cells and white blood cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving azacitidine together with darbepoetin alfa and G-CSF may be an effective treatment for myelodysplastic syndromes.
PURPOSE: This clinical trial is studying how well giving azacitidine together with darbepoetin alfa and G-CSF works in treating patients with myelodysplastic syndromes.
Detailed description
OBJECTIVES:
Primary
- Determine the hematological response rate in patients with myelodysplastic syndromes treated with azacitidine, darbepoetin alfa, and filgrastim (G-CSF).
Secondary
- Determine the time to leukemia progression, survival, and changes in apoptotic index of bone marrow in patients treated with this regimen.
OUTLINE: This is an open-label, nonrandomized study.
- Initial therapy (courses 1 and 2): Patients receive azacitidine subcutaneously (SC) or intra-venous (IV) on days 1-5 (week 1) and darbepoetin alfa* SC on day 8 (week 2). Treatment repeats every 28 days for 2 courses.
Patients undergo bone marrow aspirate and biopsy to assess response. Patients with a major hematological improvement OR with grade 3-4 hematological toxicities during the first 2 courses of therapy AND/OR ≥ 50% reduction in bone marrow cellularity compared to baseline proceed to optimization therapy A. Patients not meeting any of the above criteria proceed to optimization therapy B. Patients with disease progression are removed from study.
- Optimization therapy A (courses 3-8): Patients receive azacitidine SC or IV on days 1-5 (week 1), darbepoetin alfa** SC on day 8 (week 2), and filgrastim (G-CSF) SC 3 times weekly in weeks 2-4.
- Optimization therapy B (courses 3-8): Patients receive a higher dose of azacitidine on days 1-5 (week 1), darbepoetin alfa** SC on day 8 (week 2), and G-CSF 3 times weekly in weeks 2-4.
In both optimization therapy A and B, treatment repeats every 28 days for 6 courses. Patients with any degree of hematological improvement after initial therapy and optimization therapy proceed to maintenance therapy.
- Maintenance therapy (course 9 and all subsequent courses): Patients receive azacitidine on days 1-5 (week 1). Only patients with anemia (hemoglobin < 12 g/dL) and/or neutropenia (absolute neutrophil count < 1,500/mm ³) at the start of any given course during maintenance therapy receive darbepoetin alfa** SC beginning on day 8 (week 2) and continuing once every 21 days and G-CSF SC 3 times weekly beginning in week 2.
Courses repeat every 28-56 days (determined by the treating physician) in the absence of disease progression or unacceptable toxicity.
Bone marrow samples are obtained at baseline and after the completion of course 2 of study treatment for apoptosis analysis, flow cytometry, and gene expression profiles of p53 and p21 by immunohistochemistry. Peripheral blood samples are obtained periodically and analyzed for hemoglobin F quantitation.
NOTE: *Administered only if the patient is anemic (hemoglobin < 12 g/dL).
NOTE: **Darbepoetin alfa is held if hemoglobin > 12 g/dL on day 1 of a given cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitadine and Hematopoietic Growth Factors | Experimental | Drug: Azacitadine and Hematopoietic Growth FactorsCombination of Azacitadine andHematopoietic Growth Factors |
Who may qualify
- Ages
- Up to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| Azacitadine and Hematopoietic Growth FactorsCombination of Azacitadine and Hematopoietic Growth Factors | Drug | Azacitadine and Hematopoietic Growth Factors |
Primary outcome
Number of Participants With Complete Response
Time frame: Approximately 112 days
Complete response is normalization of abnormal blood counts, and disappearance of signs of morphological changes in the bone marrow. If the previously present cytogenetic abnormalities are absent then it is referred also as a cytogenetic complete remission.
Rate of Major Hematological Improvement
Time frame: Approximately 112 days
For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for red cell transfusion-dependent patients, transfusion independence.
5 secondary outcomes
Minor Hematological Improvements
Time frame: Approximately 112 days
Time to Progression to Acute Myeloid Leukemia (Blast ≥ 20%) or Death
Time frame: Approximately 12 months
Overall Survival
Time frame: Approximately 12 months
Change in Bone Marrow Apoptosis
Time frame: Baseline and approximately 12 months
Expression of p53 and p21
Time frame: Approximately 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
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.
Bayard L. Powell, MD principal investigator
Wake Forest University Health Sciences
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 Azacitadine and Hematopoietic Growth Factors in people with Leukemia and Myelodysplastic Syndromes, run by Wake Forest University Health Sciences 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?
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 6 Sep 2018. 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 17 Apr 2012). 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?
Number of Participants With Complete Response (time frame: Approximately 112 days). The study lists 2 primary outcomes in all. 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 6 Sep 2018.