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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA043703 | U.S. NIH Grant/Contract | View source | |
| CCF-6818 | Other Identifier | Cleveland Clinic IRB |
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| Name | Class |
|---|---|
| University of Michigan | OTHER |
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with gemtuzumab ozogamicin works in treating patients with advanced myelodysplastic syndromes.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, open-label study.
Patients receive arsenic trioxide IV over 1 hour once daily on days 1-5 in week 1 and then twice weekly in weeks 2-12. They also receive gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 12 weeks during study treatment, and then 4 weeks after the completion of study treatment.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATO + GO | Experimental | Arsenic Trioxide 0.25 mg/kg D1-5 Week 1/Twice Weekly W2-12 + Gemtuzumab Ozogamicin 3 mg/m^2 D8 for 1 or 2 Cycles of 12 Weeks each |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| arsenic trioxide | Drug | Arsenic trioxide will be administered at a dose of 0.25 mg/kg/day IV over 1-2 hours for 5 consecutive days during the first week. Subsequently, arsenic trioxide will be given at a dose of 0.25mg/kg/day twice a week for 11 additional weeks (weeks 2-12). |
| Measure | Description | Time Frame |
|---|---|---|
| Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML) | The null hypothesis to be tested was the percentage who will respond to combination arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) therapy is <10%. A total of >/= 9 responses observed in 30 evaluable patients was taken as evidence warranting further study of the regimen, provided the toxicity profile also appears favorable. The IWG Criteria standardizes the clinical responses in MDS and AML based upon hematologic improvement, quality of life and cytogenic improvement. These standardizations allow for the responses to be determined as either complete responses or partial responses. | at 12 weeks post treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Patient's Overall Survival from date of enrollment to a minimum of three years for survival. | From date of enrollment to a minimum of three years for survival |
| Tolerability | Tolerability of Therapy was assessed through use of the National Cancer Institute Common Toxicity Criteria (version 3.0). Treatment tolerability was determined based upon whether or not the physician determined therapy was in the patient's best interest, whether the patient wanted to continue therapy or not, whether patients discontinued treatment due to progressive disease, or whether patients discontinued treatment due to toxicity. |
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DISEASE CHARACTERISTICS:
Diagnosis of one of the following hematologic malignancies:
Myelodysplastic syndromes (MDS) of one of the following French-American-British (FAB) classifications:
International Prognostic Scoring System (IPSS) score of intermediate-2 or higher in the setting of > 5% myeloblasts
Acute myeloid leukemia that has evolved from MDS
Must not be a candidate for bone marrow transplantation as first-line therapy or must have declined bone marrow transplantation
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Mikkael A. Sekeres, MD, MS | The Cleveland Clinic | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio | 44195 | United States |
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Patients were enrolled at Cleveland Clinic and the University of Michigan from February 2004 through June 2006.
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| ID | Title | Description |
|---|---|---|
| FG000 | ATO (0.25mg/kg) and GO (3mg/m2) | ATO dosing was based on the phase 2 European Union regimen at a dose of 0.25 mg/kg administered intravenously on Days 1 through 5 during Week 1 and then twice weekly during Weeks 2 to 12, and GO at a dose of 3mg/m2 on Day 8 for 1 or 2 cycles of 12 weeks each. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ATO (0.25mg/kg) and GO (3mg/m2) | ATO dosing was based on the phase 2 European Union regimen at a dose of 0.25 mg/kg administered intravenously on Days 1 through 5 during Week 1 and then twice weekly during Weeks 2 to 12, and GO at a dose of 3mg/m2 on Day 8 for 1 or 2 cycles of 12 weeks each. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML) | The null hypothesis to be tested was the percentage who will respond to combination arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) therapy is <10%. A total of >/= 9 responses observed in 30 evaluable patients was taken as evidence warranting further study of the regimen, provided the toxicity profile also appears favorable. The IWG Criteria standardizes the clinical responses in MDS and AML based upon hematologic improvement, quality of life and cytogenic improvement. These standardizations allow for the responses to be determined as either complete responses or partial responses. | Responses According to IWG MDS Criteria (n=30) Responses According to IWG AML Criteria (n=12) | Posted | Number | percentage of patients | at 12 weeks post treatment |
|
12 Weeks of Therapy
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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 | ATO (0.25mg/kg) and GO (3mg/m2) | ATO dosing was based on the phase 2 European Union regimen at a dose of 0.25 mg/kg administered intravenously on Days 1 through 5 during Week 1 and then twice weekly during Weeks 2 to 12, and GO at a dose of 3mg/m2 on Day 8 for 1 or 2 cycles of 12 weeks each. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mikkael Sekeres, MD, MS | The Cleveland Clinic | 216-445-9353 | sekerem@ccf.org |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D009190 | Myelodysplastic Syndromes |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000077237 | Arsenic Trioxide |
| D000079982 | Gemtuzumab |
| ID | Term |
|---|---|
| D001152 | Arsenicals |
| D007287 | Inorganic Chemicals |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
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|
| gemtuzumab ozogamicin | Drug | Gemtuzumab ozogamicin consists of a 2 hr infusion at a dose of 3mg/m2 on day 8 of each 12-week cycle. Gemtuzumab ozogamicin should be administered at a minimum of one hour after the completion of the arsenic trioxide infusion |
|
|
| 12 Weeks |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Arsenic Trioxide 0.25 mg/kg D1-5 Week 1/Twice Weekly W2-12 + Gemtuzumab Ozogamicin 3 mg/m^2 D8 for 1 or 2 Cycles of 12 Weeks each
arsenic trioxide: Arsenic trioxide will be administered at a dose of 0.25 mg/kg/day IV over 1-2 hours for 5 consecutive days during the first week. Subsequently, arsenic trioxide will be given at a dose of 0.25mg/kg/day twice a week for 11 additional weeks (weeks 2-12).
gemtuzumab ozogamicin: Gemtuzumab ozogamicin consists of a 2 hr infusion at a dose of 3mg/m2 on day 8 of each 12-week cycle. Gemtuzumab ozogamicin should be administered at a minimum of one hour after the completion of the arsenic trioxide infusion
|
|
| Secondary | Overall Survival | Patient's Overall Survival from date of enrollment to a minimum of three years for survival. | Posted | Median | Full Range | months | From date of enrollment to a minimum of three years for survival |
|
|
|
| Secondary | Tolerability | Tolerability of Therapy was assessed through use of the National Cancer Institute Common Toxicity Criteria (version 3.0). Treatment tolerability was determined based upon whether or not the physician determined therapy was in the patient's best interest, whether the patient wanted to continue therapy or not, whether patients discontinued treatment due to progressive disease, or whether patients discontinued treatment due to toxicity. | Posted | Number | participants | 12 Weeks |
|
|
|
| 19 |
| 30 |
| 28 |
| 30 |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea / Vomiting / Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea / Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| QT / QTc Interval Prolongation | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash / Pruritis | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea / Vomiting / Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea / Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia / Decreased Appetite | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pyrexia | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Insomnia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Catheter / Infusion Site Disorders / Infections | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Abdominal Pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cardiac Arrhythmia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| QT / QTc Interval Prolongation | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chills / Rigors | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness / Vertigo | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ecchymosis / Petechiae | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D001855 | Bone Marrow Diseases |
| D000753 | Anemia, Refractory |
| D000740 | Anemia |
| D007951 | Leukemia, Myeloid |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000080084 |
| Calicheamicins |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Discontinue Tx During C1: Progressive Disease |
|
| Discontinue Tx During C1:Treatment Toxicity |
|
| Discontinue Tx After C1: Progressive Disease |
|
| Discontinue Tx After C1: Treatment Toxicity |
|