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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-00263 | Registry Identifier | NCI CTRP |
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| Name | Class |
|---|---|
| Genzyme, a Sanofi Company | INDUSTRY |
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The goal of this clinical research study is to learn if sequential administration of decitabine and clofarabine can help to control MDS better than decitabine alone. The safety of this drug combination will also be studied.
The Study Drugs:
Decitabine is designed to damage cells' DNA (genetic material), which may cause myelodysplastic marrow cells to work more like normal marrow cells.
Clofarabine is designed to interfere with the growth and development of abnormal marrow cells.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups.
Study Drug Administration:
Each cycle is 4-8 weeks depending on how you tolerate the drug and how the MDS responds to it.
Group 1:
If you are in Group 1, you will receive the drugs in an alternating series of cycles. This means that you will receive decitabine for the first 3 cycles, then clofarabine for the next 3 cycles, and then repeat. This pattern will continue for up to 24 cycles.
On Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21, you will receive decitabine by vein over 1-2 hours.
On Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24, you will receive clofarabine by vein over 1-2 hours.
Group 2:
If you are in Group 2, you will receive decitabine by vein over 1-2 hours on Days 1-5 of every cycle.
Study Visits:
On Day 1 of every cycle, the following tests and procedures will be performed:
Once a week, blood (about 1-2 teaspoons) will be drawn for routine tests.
At the end of Cycle 3, you will have a bone marrow aspirate to check the status of the disease.
If the disease has not gone into remission after Cycle 3, your next bone marrow aspirate will depend on your group. If you are in Group 1, you may have another aspirate about 3 weeks after you begin Cycle 4. After that, you may have an aspirate every 2 weeks (or more often if your doctor feels it is needed) until the response (or lack thereof) is confirmed. If you are in Group 2, you may not have another bone marrow aspirate until after the end of Cycle 6.
You will need to stay in Houston to receive the study drug(s). When you have study visits where you are not receiving study drug(s), these tests can be performed by your local doctor. If your MD Anderson leukemia doctor approves, your study drug can be administered outside MD Anderson by your local doctor.
Length of Study:
You will be on study for up to 24 cycles. You will be taken off study early if the disease gets worse or you experience any intolerable side effects.
Follow-up Visits:
After your last dose of study drug, you will have follow-up visits. You will only have these visits if the disease has responded to the study drug.
This is an investigational study. Clofarabine is FDA approved and commercially available for use in pediatric patients with a type of blood cancer (acute lymphocytic leukemia -- ALL). Its use in patients with MDS is investigational.
Decitabine is FDA approved and commercially available for use in patients with MDS.
Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Decitabine + Clofarabine | Experimental | Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m^2 five days for next 3 cycles), pattern repeats for up to 24 cycles. |
|
| Decitabine | Experimental | Decitabine 20 mg/m^2 IV daily for 5 days for a total of 24 courses. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Decitabine | Drug | Decitabine 20 mg/m^2 by vein daily over 1-2 hours for 5 days for both Group 1 and Group 2. Group 1 receives decitabine on Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21; and Group 2 is on Days 1-5 of every cycle. |
| Measure | Description | Time Frame |
|---|---|---|
| Event Free Survival (EFS) at 1 Year | Percentage of participants with event free survival at 1 year. Event free survival (EFS) where event is defined as either death or transformation to acute myeloid leukemia (AML) (marrow and/or blood blasts >/= 20%) | Assessed at 12 months/1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Participant Response | Responses: Complete Remission (CR): Normalization peripheral blood & bone marrow </= 5% bone marrow blasts, no evidence dysplasia; peripheral blood granulocyte >/= 1.0 x 10^9/L, & platelet>/= 100 x 10^9/L. Partial Remission: all CR criteria if abnormal before treatment except marrow blasts decrease =/> 50% compared to pretreatment or a less-advanced MDS disease classification than prior to treatment. Hematologic Improvement: Response maintained 8+ weeks: Hemoglobin (pretreatment < 11 g/dL): improves 1.5 g/dL or reduced by 4 units of red blood cell (RBC) transfusions in 8 weeks compared with pretreatment transfusions in 8 weeks; or Platelet (pretreatment < 100 x 10^9/L): absolute increase >/= 30 x 10^9/L, starting platelet > 20 x 10^9/L OR increase < 20 x 10^9/L to > 20 x 10^9/L and =/> 100%. Neutrophil (pretreatment < 1 x 10^9/L): increase 100% & absolute increase > 0.5 x 10^9/L. |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Guillermo Garcia-Manero, M.D. | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Website | View source |
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Of the 42 participant enrolled, five were not randomized or treated and are therefore excluded from the trial details. One participant included in group assignment was randomized but not treated as a result of early death.
Recruitment period: January 28, 2010 to May 7, 2014. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | Decitabine + Clofarabine | Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m^2 five days for next 3 cycles), pattern repeats for up to 24 cycles. |
| FG001 | Decitabine | Decitabine 20 mg/m^2 IV daily for 5 days for a total of 24 courses. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Decitabine + Clofarabine | Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m^2 five days for next 3 cycles), pattern repeats for up to 24 cycles. |
| BG001 | Decitabine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Event Free Survival (EFS) at 1 Year | Percentage of participants with event free survival at 1 year. Event free survival (EFS) where event is defined as either death or transformation to acute myeloid leukemia (AML) (marrow and/or blood blasts >/= 20%) | One of 18 participants in the Decitabine arm was not treated due to early death thus is excluded from analysis. | Posted | Number | percentage of participants | Assessed at 12 months/1 year |
|
Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Decitabine + Clofarabine | Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m^2 five days for next 3 cycles), pattern repeats for up to 24 cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lung Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary tract infection (UTI) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Guillermo Garcia-Manero, MD / Professor, Leukemia | The University of Texas (UT) MD Anderson Cancer Center | 713-745-3428 | ggarciam@mdanderson.org |
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| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D000077209 | Decitabine |
| D000077866 | Clofarabine |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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|
| Clofarabine | Drug | Clofarabine 10 mg/m^2 by vein daily over 1-2 hours for 5 days on Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24. |
|
|
| Up to 6 months |
| Physician Decision |
|
| Death |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Off treatment for long period |
|
Decitabine 20 mg/m^2 IV daily for 5 days for a total of 24 courses. |
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Decitabine 20 mg/m^2 IV daily for 5 days for a total of 24 courses. |
|
|
| Secondary | Participant Response | Responses: Complete Remission (CR): Normalization peripheral blood & bone marrow </= 5% bone marrow blasts, no evidence dysplasia; peripheral blood granulocyte >/= 1.0 x 10^9/L, & platelet>/= 100 x 10^9/L. Partial Remission: all CR criteria if abnormal before treatment except marrow blasts decrease =/> 50% compared to pretreatment or a less-advanced MDS disease classification than prior to treatment. Hematologic Improvement: Response maintained 8+ weeks: Hemoglobin (pretreatment < 11 g/dL): improves 1.5 g/dL or reduced by 4 units of red blood cell (RBC) transfusions in 8 weeks compared with pretreatment transfusions in 8 weeks; or Platelet (pretreatment < 100 x 10^9/L): absolute increase >/= 30 x 10^9/L, starting platelet > 20 x 10^9/L OR increase < 20 x 10^9/L to > 20 x 10^9/L and =/> 100%. Neutrophil (pretreatment < 1 x 10^9/L): increase 100% & absolute increase > 0.5 x 10^9/L. | One of 18 participants in the Decitabine arm was not treated due to early death thus is excluded from analysis. | Posted | Number | participants | Up to 6 months |
|
|
|
| 1 |
| 19 |
| 19 |
| 19 |
| EG001 | Decitabine | Decitabine 20 mg/m^2 IV daily for 5 days for a total of 24 courses. | 1 | 18 | 18 | 18 |
| Bacteremia - Escherichia coli (E. coli) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Septic Shock, Bacteremia |
|
| Death | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bacteremia -E. Coli | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Bacteremia-pseudomonas | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Bilateral joint pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bilateral lower lobe pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Chest Pain | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Deep vein thrombosis -picc line | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fracture-femoral neck | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Gastrointestinal Bleed | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection - other | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Intracranial hemorrhage | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Left side weakness | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Respiratory infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Lung Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness in lower limbs | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash-extremities | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tumor Lysis Syndrome | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vancomycin-resistant enterococci (VRE) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| sinusitis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D009369 | Neoplasms |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D000227 | Adenine Nucleotides |
| D011685 | Purine Nucleotides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D001087 | Arabinonucleosides |
| D009711 | Nucleotides |
| D012265 | Ribonucleotides |
| Hematologic Improvement (HI) |
|