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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-02439 | Registry Identifier | NCI CTRP |
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Study was stopped by the principal investigator due to nonsatisfactory clinical benefit even in patients treated at the highest dose (200 mg ).
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| Name | Class |
|---|---|
| Incyte Corporation | INDUSTRY |
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The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with acute leukemia and to learn if the study drug can help control the disease. The safety of the drug will also be studied.
The Study Drug:
Ruxolitinib is designed to block a gene mutation that may be important in cancer cell growth and survival. By blocking the gene mutation, this may cause the cancer cells to die.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 30 participants will be enrolled in the Phase I portion of the study, and up to 136 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of ruxolitinib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of ruxolitinib. Each new group will receive a higher dose of ruxolitinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ruxolitinib is found.
If you are enrolled in the Phase II portion, you will receive ruxolitinib at the highest dose that was tolerated in the Phase I portion or at a lower dose.
Study Drug Administration:
You will take ruxolitinib tablet(s) by mouth 2 times a day on Days 1-28 of each 28-day study cycle.
You will be asked to keep a diary to record the doses taken. You will be asked to bring your diary and any unused drug to your next visit.
Study Visits:
On Days 1, 7, 14, and 21 of Cycle 1:
On Day 1 of Cycle 2:
During Cycles 2 and beyond, blood (about 2 teaspoons) will be drawn for routine tests at least every 1-2 weeks. This blood may be drawn at a clinic close to your home.
On Day 1 of Cycles 3, 6, 9, and beyond:
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.
Your participation on the study will be over once you have completed the end-of-study visit and the follow-up call.
End-of-Study Visit:
After your last dose of study drug, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:
Follow-Up:
About one month after your end-of-study visit, the study staff will call and ask about any side effects you may be having. This call should last about 5 minutes.
This is an investigational study. Ruxolitinib is FDA approved and commercially available for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis. Its use to treat acute leukemia is investigational.
Up to 166 patients will take part in this study. All will be enrolled at MD Anderson.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ruxolitinib 50 mg BID | Experimental | Phase I - Starting dose of Ruxolitinib 50 mg by mouth twice a day for 28 day cycle. |
|
| Ruxolitinib 100 mg BID | Experimental | Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle. |
|
| Ruxolitinib 200 mg BID | Experimental | Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ruxolitinib | Drug | Phase I - Starting dose of 50 mg by mouth twice a day for 28 day cycle. Phase II - MTD reached in Phase I. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | MTD defined as highest dose level at which no more than one out of six subject experiences dose limiting toxicity (DLT) during first cycle (28 days) of therapy. A non-hematologic DLT defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to Common Toxicity Criteria for Adverse Effects (CTCAE) criteria) assessed as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during first 28 days on study. Participants who received at least 80% of the originally assigned doses in the first cycle were evaluable for DLT assessment of each cohort. | End of first 28 day cycle for toxicity |
| Maximum Tolerated Dose (MTD) of Ruxolitinib | The MTD is defined as the highest dose level at which no more than one out of six subject experiences DLT during the first cycle (28 days) of therapy. | End of first 28 day cycle |
| Measure | Description | Time Frame |
|---|---|---|
| Participants With a Response | Response is defined as complete remission (CR) + complete remission with incomplete blood count (CRi) + Hematologic improvement (HI). Response was to be assessed for participants who were evaluated for the Phase II portion of this study. CR is absolute neutrophil count (ANC) >/= 1x109/L and platelet count >/= 100x109/L, absence of leukemia blast cells, normal marrow differential, and complete resolution of extramedullary disease. CRi is CR but platelets are < 100x109/L or ANC is <1x109/L. HI is described by the number of individual, positively affected cell lines without the use of growth factors and/or transfusions (lasting at least 4 weeks). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Srdan Verstovsek, MD | 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 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25441108 | Derived | Pemmaraju N, Kantarjian H, Kadia T, Cortes J, Borthakur G, Newberry K, Garcia-Manero G, Ravandi F, Jabbour E, Dellasala S, Pierce S, Verstovsek S. A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):171-6. doi: 10.1016/j.clml.2014.08.003. Epub 2014 Sep 17. |
| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Website | View source |
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Recruitment Period: December 9, 2010 to September 26, 2012. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ruxolitinib 50 mg BID | Phase I starting dose of Ruxolitinib 50 mg by mouth twice a day (BID) for 28 day cycle. |
| FG001 | Ruxolitinib 100 mg BID | Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle. |
| FG002 | Ruxolitinib 200 mg BID | Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ruxolitinib 50 mg BID | Phase I starting dose of Ruxolitinib 50 mg by mouth twice a day (BID) for 28 day cycle. |
| BG001 | Ruxolitinib 100 mg BID | Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle. |
| 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 | Number of Participants With Dose Limiting Toxicities (DLTs) | MTD defined as highest dose level at which no more than one out of six subject experiences dose limiting toxicity (DLT) during first cycle (28 days) of therapy. A non-hematologic DLT defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to Common Toxicity Criteria for Adverse Effects (CTCAE) criteria) assessed as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during first 28 days on study. Participants who received at least 80% of the originally assigned doses in the first cycle were evaluable for DLT assessment of each cohort. | Posted | Count of Participants | Participants | End of first 28 day cycle for toxicity |
|
Adverse events collected during 28 day cycle, up to 9 cycles.
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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 | Ruxolitinib 50 mg BID | Phase I starting dose of Ruxolitinib 50 mg by mouth twice a day (BID) for 28 day cycle. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin Increased | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Srdan Verstovsek, Professor, Leukemia | The University of Texas (UT) MD Anderson Cancer Center | 713-792-7734 | CR_Study_Registration@mdanderson.org |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C540383 | ruxolitinib |
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Phase I is a standard 3+3 design and will be used to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and no formal evaluation of efficacy (response rate will be implemented. Patients in Phase I part who were treated at the MTD will be included toward patients assessed for response in the phase II stage.
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|
| Up to 1 year |
| BG002 | Ruxolitinib 200 mg BID | Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Ruxolitinib 100 mg BID | Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle. |
| OG002 | Ruxolitinib 200 mg BID | Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle. |
|
|
| Primary | Maximum Tolerated Dose (MTD) of Ruxolitinib | The MTD is defined as the highest dose level at which no more than one out of six subject experiences DLT during the first cycle (28 days) of therapy. | Posted | Number | mg | End of first 28 day cycle |
|
|
|
| Secondary | Participants With a Response | Response is defined as complete remission (CR) + complete remission with incomplete blood count (CRi) + Hematologic improvement (HI). Response was to be assessed for participants who were evaluated for the Phase II portion of this study. CR is absolute neutrophil count (ANC) >/= 1x109/L and platelet count >/= 100x109/L, absence of leukemia blast cells, normal marrow differential, and complete resolution of extramedullary disease. CRi is CR but platelets are < 100x109/L or ANC is <1x109/L. HI is described by the number of individual, positively affected cell lines without the use of growth factors and/or transfusions (lasting at least 4 weeks). | The study was stopped because of a lack of satisfactory clinical benefit, and did not go on to the Phase II portion. Therefore, data were not collected for this outcome measure. | Posted | Up to 1 year |
|
|
| 4 |
| 4 |
| 4 |
| 4 |
| EG001 | Ruxolitinib 100 mg BID | Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle. | 5 | 5 | 5 | 5 |
| EG002 | Ruxolitinib 200 mg BID | Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle. | 18 | 18 | 18 | 18 |
| Alveolar hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cerebral edema and mass | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Death | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutropenia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Stroke | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophils count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Platelets decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Ventricular arrhythmia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constiptation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage pulmonary | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema: head and neck | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema: limb | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alkaline phosphatase Increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Alanine aminotransferase increased (ALT) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased (AST) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Creatinine Increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Central Nervous System Ischemia | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neurology-Other Issues | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Speech impairment | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| PULMONARY INFILTRATES | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hot Flash | Reproductive system and breast disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infections | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
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| D007951 | Leukemia, Myeloid |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |