- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00674479
INCB018424 in Patients With Advanced Hematologic Malignancies
Phase II Study of INCB018424 in Patients With Advanced Hematologic Malignancies
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The Study Drug:
Ruxolitinib is designed to block the protein product of a mutated (changed) gene that may be important in cancer cell growth and survival.
Study Drug Administration:
If you are found to be eligible to take part in this study, every day of each 28-day cycle you will take ruxolitinib by mouth 2 times a day (in the morning and evening).
On Day 1 of each cycle, the morning dose of study drug should not be taken until you visit the clinic unless the doctor says differently.
If the doctor thinks it is necessary, your dose of study drug may be raised or lowered.
Study Visits:
On Day 1 of Cycle 1, the following tests and procedures will be performed:
- You will be asked to list any drugs you may be taking and if you have experienced any side effects.
- You will have a physical exam, including measurement of your vital signs.
On Days 8, 15, and 22 of Cycle 1 (+/- 2 days), the following tests and procedures will be performed (these can be done at your local physician's office):
- Your medical history will be reviewed, including any drugs you may be taking.
- You will be asked if you have experienced any side effects.
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 2 tablespoons) will be drawn for routine tests.
On Day 1 of Cycles 2-4 (+/- 2 days) and then once every 3 months, the following tests and procedures will be performed:
- Your medical history will be reviewed, including any drugs you may be taking.
- You will be asked if you have experienced any side effects.
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If the doctor thinks it is necessary, blood (about 1 tablespoon) will be drawn to check the status of the disease.
- If the doctor thinks it is necessary, you will have a bone marrow biopsy/aspirate to check the status of the disease.
- During these visits, you will also be receiving your new supply of medication.
On Days 8, 15, and 22 of Cycles 2 and 3, blood (about 2 tablespoons) will be drawn for routine tests at your local doctor's office.
On Day 1 of Cycles 4, 7, and every 6th cycle after that (Cycles 13, 19, 25, and so on), you will have a bone marrow aspiration or biopsy to check the status of the disease. On Day 1 of Cycle 4, the bone marrow aspiration/biopsy will also look at the genes and chromosomes of the leukemia cells. If there is not enough information from the biopsy/aspirate, leftover blood will be used to look at this gene and chromosome information.
Every 2 weeks of Cycles 4-7, blood (about 2 tablespoons) will be drawn for routine tests.
You will be called once a month while you are on study. During this phone call you will be asked how you are doing, if you have experienced any side effects, and if you are taking the study drug at the correct dose and time. This phone call will take a few minutes. You will be sent a card in the mail to remind you about any study visits you need to complete.
Women who are able to become pregnant will have a urine pregnancy test if there is a suspicion of pregnancy. If the test is positive, they will then have a blood (about 1 teaspoon) pregnancy test.
Length of Study:
You may stay on study for as long as you are benefitting. You will be taken off study if you experience intolerable side effects or the disease gets worse.
End-of-Study Visit:
After you go off study you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:
- Your medical history will be reviewed, including any drugs you may be taking.
- You will be asked if you have experienced any side effects.
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- Blood (about 2 tablespoons) will be drawn for routine tests.
- If the doctor thinks it is necessary, blood (about 1 tablespoon) will be drawn to check the status of the disease.
- If the doctor thinks it is necessary, you will have a bone marrow biopsy/aspirate to check the status of the disease.
- Women who are able to become pregnant will have a urine pregnancy test. If the test is positive, they will then have a blood (about 1 teaspoon) pregnancy test.
This is an investigational study. Ruxolitinib is FDA approved and commercially available to treat myelofibrosis. Giving ruxolitinib to patients with advanced hematological malignancies is investigational.
Up to 120 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- University of Texas MD Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Must be at least 18 years of age.
- Patients must have relapsed/refractory leukemias for which no standard therapies exist. Patients with poor-risk myelodysplasia (MDS) and chronic myelomonocytic leukemia (CMML) who failed prior therapy are also candidates for this protocol. Relapsed/refractory leukemias include acute non-lymphocytic leukemia (AML) by World Health Organization (WHO) classification (i.e. >/= 20% blasts), acute lymphocytic leukemia (ALL), or chronic myelogenous leukemia (CML) in blast crisis. Patients with CML who are resistant to at least two tyrosine kinase inhibitors and have no standard stem cell transplant option are also eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- A female of childbearing potential must have a negative serum or urine pregnancy test at screening. Women of child-bearing potential must use acceptable contraceptive methods, and must have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods for the duration of time on study.
- Must be able and willing to give written informed consent.
- In the absence of rapidly progressing disease, the interval from prior treatment to time of study drug administration should be at least 2 weeks for cytotoxic agents, or at least one week for noncytotoxic agents. Persistent clinically significant toxicities from prior chemotherapy must not be greater than grade 2.
- Patients must have the following clinical laboratory values unless considered due to leukemic organ involvement: 1.) Serum creatinine less than or equal to 2.0 mg/dl. 2.) Total bilirubin less than or equal to 1.5x the upper limit of normal unless considered due to Gilbert's syndrome or hemolysis. 3.) Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 2.5x the upper limit of normal unless considered due to organ leukemic involvement (then 5x).
- Patients with active central nervous system (CNS) disease are included and will be treated concurrently with intrathecal therapy. INCB018424 will not be administered by intrathecal route.
Exclusion Criteria:
- Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Active heart disease including myocardial infarction within the previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure.
- Current treatment or treatment within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of study medication with another investigational medication or current enrollment in another investigational drug protocol (unless there is evidence of rapidly progressive disease in which case a shorter interval from last therapy may be acceptable).
- Females who are pregnant or are currently breastfeeding.
- Patients receiving therapy with intermediate or high dose steroids greater than the equivalent of 10 mg prednisone per day are not allowed.
- Evidence of active hepatitis or human immunodeficiency virus (HIV) infection determined by screening laboratory test results or results within prior 3 months.
- Any unresolved toxicity equal to or greater than Grade 2 from previous anticancer therapy, except for stable chronic toxicities not expected to resolve, such as peripheral neurotoxicity.
- Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks prior to study entry, excluding the placement of vascular access.
- Uncontrolled intercurrent illness or any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.
- In patients who are receiving medications known to be inhibitors or inducers of CYP3A4 every effort will be made to change these medications to acceptable alternatives. If this is not safely possible, patients will be excluded from participation in the study. If a patient is already on the study, must be started on a CYP3A4 inhibitor, and is demonstrating benefit from the study, they will be seen twice weekly in the first cycle and weekly in the subsequent cycles for toxicity evaluation and their dose will be modified in the event of a toxicity related to the study drug.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: INCB018424
The starting dose of INCB018424 will be 25 mg by mouth twice daily.
|
Starting dose: 25 mg by mouth (po) twice daily for 7 days each week for 4 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response Rate
Time Frame: Patients will be evaluated after each full cycle of therapy (28 days) for response.
|
"Time of Response " defined as the period of time from the date of first study drug administration until the first objective documentation of response.
Clinical response is defined as Complete remission (CR) + Partial remission (PR) + CRp + Hematologic Improvement (HI).
Participants in CR must be free of all symptoms related to leukemia and have an absolute neutrophil count (ANC) >/= 1x10^9/L, platelet count ./+
100x10^9, normal marrow differential (</= 5% blasts).
Partial remission (PR) is CR with 6-25% abnormal cells in the marrow or 50% decrease in marrow blasts.
CRp is CR but platelet count < 100x10^9/L.
HI is defined as for patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence.
|
Patients will be evaluated after each full cycle of therapy (28 days) for response.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To Determine the Pharmacokinetics (PK) Activity
Time Frame: Up to 3 months
|
Exploratory sampling will be done to determine the INCB018424 PK profile.
The PK parameters of INB018424 will be summarized using descriptive statistics, and the log-transformed INCB018424 PK parameters will be compared using a 1-factor analysis of variance.
The mean values of the PK parameters may be compared to historical data in healthy volunteers to determine if the INCB018424 PK profile is different between patients with hematological malignancies and healthy patients.
|
Up to 3 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To Determine Pharmacodynamics Activity Including the Modulation of Signal Transducer and Activator of Transcription (STAT) Protein Phosphorylation.
Time Frame: Up to 3 months
|
The PD parameters will be calculated to explore preliminary evidence of PD activity by assessing the effect of INCB018424 on pre- and post-dose.
If the p-STAT3/5 signaling data are sufficiently robust, an exploratory PK/PD analysis will be performed.
|
Up to 3 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Farhad Ravandi-Kashani, M.D., M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Precancerous Conditions
- Chronic Disease
- Neoplasms
- Myelodysplastic Syndromes
- Hematologic Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Other Study ID Numbers
- 2007-0925
- NCI-2012-01616 (Registry Identifier: NCI CTRP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Myeloid Leukemia
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Jacqueline Garcia, MDEli Lilly and CompanyCompletedCombination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid LeukemiaRelapsed Adult Acute Myeloid Leukemia | Refractory Adult Acute Myeloid LeukemiaUnited States
-
Terrence J Bradley, MDImago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New...RecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia, in RelapseUnited States
-
University of NebraskaNational Cancer Institute (NCI)Active, not recruitingSecondary Acute Myeloid Leukemia | Therapy-Related Acute Myeloid Leukemia | Adult Acute Myeloid LeukemiaUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Massachusetts General HospitalExelixisCompletedRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
Washington University School of MedicineWithdrawnRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
C. Babis AndreadisGateway for Cancer Research; AVEO Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
Xuzhou Medical UniversityRecruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia RefractoryChina
Clinical Trials on INCB018424
-
Incyte CorporationApproved for marketingGraft-versus-host Disease (GVHD)
-
Incyte CorporationNo longer available
-
Incyte CorporationApproved for marketingGraft-versus-host Disease (GVHD)United States
-
Incyte CorporationCompletedMyelofibrosisUnited States
-
Incyte CorporationRecruiting
-
Incyte CorporationCompleted
-
M.D. Anderson Cancer CenterIncyte CorporationCompletedLeukemiaUnited States
-
Incyte CorporationCompletedVitiligoUnited States, Canada, Poland, Spain, Germany, Bulgaria, France, Netherlands
-
Incyte CorporationCompletedAtopic DermatitisUnited States