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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2013-01097 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| J1319 | Other Identifier | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | |
| 9362 | Other Identifier | CTEP | |
| U01CA070095 | U.S. NIH Grant/Contract | View source | |
| P30CA006973 | U.S. NIH Grant/Contract | View source |
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This randomized phase II trial studies how well cytarabine with or without SCH 900776 works in treating adult patients with relapsed acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. SCH 900776 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cytarabine is more effective with or without SCH 900776 in treating acute myeloid leukemia.
PRIMARY OBJECTIVES:
I. To compare the rates of complete remission (CR) plus CR with incomplete recovery (CRi) achieved with cytosine arabinoside (ara-C) (cytarabine) plus the checkpoint kinase 1 (CHK1) inhibitor MK-8776 (Chk1 inhibitor SCH 900776) vs. ara-C alone for adults (ages 18-75) with relapsed acute myelogenous leukemia (AML).
SECONDARY OBJECTIVES:
I. To evaluate and compare the toxicities of ara-C + MK-8776 vs. ara-C alone. II. To determine the disease free and overall survival of those achieving response to treatment.
III. To determine the impact of MK-8776 on AML blast cell deoxyribonucleic acid (DNA) repair protein expression profiles and correlate the expression profiles with CR/CRi in response to ara-C + MK-8776 vs. ara-C alone.
IV. To evaluate and compare the amount of DNA damage induced in AML blasts by ara-C + MK-8776 vs. ara-C.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cytarabine intravenously (IV) continuously over 72 hours on days 1-3 and 10-12 and Chk1 inhibitor SCH 900776 IV over 30 minutes on days 2, 3, 11, and 12.
ARM B: Patients receive cytarabine as in Arm A.
In both arms, courses may repeat every 28 days.
After completion of study treatment, patients are followed up periodically.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (cytarabine, Chk1 inhibitor SCH 900776) | Experimental | Patients receive cytarabine IV continuously over 72 hours on days 1-3 and 10-12 and Chk1 inhibitor SCH 900776 IV over 30 minutes on days 2, 3, 11, and 12. |
|
| Arm B (cytarabine) | Active Comparator | Patients receive cytarabine as in Arm A. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cytarabine | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate(CR/CRi) Rate | For descriptive purposes, the CR/CRi (complete response/Complete response with incomplete blood count recovery) rate will be reported at the end of the study separately for Arm A and Arm B. Responses are following definitions consistent with those published by Dohner H, Estey EH, Amadori S, et al. CR is defined as Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blasts in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. CRi: All CR criteria except for residual neutropenia (ANC < 1000/μL) | Up to 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| B. Smith | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Arizona | Scottsdale | Arizona | 85259 | United States | ||
| Blood and Marrow Transplant Group of Georgia |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A (Cytarabine, Chk1 Inhibitor SCH 900776) | Patients receive cytarabine IV continuously over 72 hours on days 1-3 and 10-12 and Chk1 inhibitor SCH 900776 IV over 30 minutes on days 2, 3, 11, and 12. Cytarabine: Given IV CHK1 Inhibitor SCH 900776: Given IV Laboratory Biomarker Analysis: Correlative studies |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| CHK1 Inhibitor SCH 900776 | Drug | Given IV |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Atlanta |
| Georgia |
| 30342 |
| United States |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | Baltimore | Maryland | 21231 | United States |
| Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | 21287 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Arm B (Cytarabine) |
Patients receive cytarabine as in Arm A. Cytarabine: Given IV Laboratory Biomarker Analysis: Correlative studies |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A (Cytarabine, Chk1 Inhibitor SCH 900776) | Patients receive cytarabine IV continuously over 72 hours on days 1-3 and 10-12 and Chk1 inhibitor SCH 900776 IV over 30 minutes on days 2, 3, 11, and 12. Cytarabine: Given IV CHK1 Inhibitor SCH 900776: Given IV Laboratory Biomarker Analysis: Correlative studies |
| BG001 | Arm B (Cytarabine) | Patients receive cytarabine as in Arm A. Cytarabine: Given IV Laboratory Biomarker Analysis: Correlative studies |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| 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 | Response Rate(CR/CRi) Rate | For descriptive purposes, the CR/CRi (complete response/Complete response with incomplete blood count recovery) rate will be reported at the end of the study separately for Arm A and Arm B. Responses are following definitions consistent with those published by Dohner H, Estey EH, Amadori S, et al. CR is defined as Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blasts in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. CRi: All CR criteria except for residual neutropenia (ANC < 1000/μL) | Posted | Number | participants | Up to 3 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 | Arm A (Cytarabine, Chk1 Inhibitor SCH 900776) | Patients receive cytarabine IV continuously over 72 hours on days 1-3 and 10-12 and Chk1 inhibitor SCH 900776 IV over 30 minutes on days 2, 3, 11, and 12. Cytarabine: Given IV CHK1 Inhibitor SCH 900776: Given IV Laboratory Biomarker Analysis: Correlative studies | 2 | 14 | 14 | 14 | ||
| EG001 | Arm B (Cytarabine) | Patients receive cytarabine as in Arm A. Cytarabine: Given IV Laboratory Biomarker Analysis: Correlative studies | 6 | 18 | 18 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Acute Kidney Injusry | Renal and urinary disorders | Systematic Assessment |
| ||
| Cardiac arrhythmia | Cardiac disorders | Systematic Assessment |
| ||
| death multi system organ failure | General disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
| ||
| acute kidney injury | Renal and urinary disorders | Non-systematic Assessment |
| ||
| ADVERSE_EVENTS 9362 9362-GA079-129 1 Investigations Alkaline phosphatase increased | Investigations | Non-systematic Assessment |
| ||
| Aspartate aminotransferase increased | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Non-systematic Assessment |
| ||
| Atelectasis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bruising | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Non-systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Colonic hemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Creatinine increased | Investigations | Non-systematic Assessment |
| ||
| delerium | Psychiatric disorders | Systematic Assessment |
| ||
| diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Depression | Psychiatric disorders | Systematic Assessment |
| ||
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dysgeusia | Nervous system disorders | Systematic Assessment |
| ||
| Electrocardiogram QT corrected interval prolonged | Investigations | Non-systematic Assessment |
| ||
| Erythroderma | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| edema limbs | General disorders | Systematic Assessment |
| ||
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Febrile Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| fever | General disorders | Systematic Assessment |
| ||
| Gastroesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
| ||
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypermagnesemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypertension | Vascular disorders | Non-systematic Assessment |
| ||
| Hallucinations | Psychiatric disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Hemolysis | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Hemorrhoids | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypoalbuminemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Hypomagnesemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Hypophosphatemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Infusion related reaction | General disorders |
| |||
| INR increased | Investigations | Non-systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Mucositis ora | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
| ||
| Phlebitis infective | Infections and infestations | Systematic Assessment |
| ||
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sinusitis | Infections and infestations | Systematic Assessment |
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| Sinus Tachycardia | Cardiac disorders | Systematic Assessment |
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| Skin Infection | Infections and infestations | Systematic Assessment |
| ||
| Tooth infection | Infections and infestations | Systematic Assessment |
| ||
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Tumor Lysis Syndrome | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Urinary Incontinence | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| B. Douglas Smith | Sidney Kimmel Comprehensive Cancer Center | (410) 287-2935 | bdsmith@JHMI.edu |
| ID | Term |
|---|---|
| D007947 | Leukemia, Megakaryoblastic, Acute |
| D007948 | Leukemia, Monocytic, Acute |
| D015479 | Leukemia, Myelomonocytic, Acute |
| D015470 | Leukemia, Myeloid, Acute |
| D004915 | Leukemia, Erythroblastic, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
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| ID | Term |
|---|---|
| D003561 | Cytarabine |
| C559815 | MK-8776 |
| ID | Term |
|---|---|
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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| >=65 years |
|
| Male |
|