- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04006847
Omega -3 Fatty Acid in Combination With Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Effect of Omega-3 Fatty Acid, Eicosapentaenoic Acid, and Its Metabolites in Combination With Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia in Stable Chronic Phase
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Hershey, Pennsylvania, United States, 17033
- Penn State Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female ≥18 years of age.
- Confirmed diagnosis of CML ≥ 18 months from diagnosis.
- Current concomitant treatment with TKI therapy (Imatinib, Dasatinib, Nilotinib or Bosutinib; excluding Ponatinib). TKI therapy should be stable (same drug and dose) for at least 3 months prior to study enrollment.
One of the following confirmed:
- BCR-ABL p210 at stable molecular disease (e.g., MMR stable but not CMR)
- HR but no MMR.
- Stable molecular response defined as 2 sequential BCR-ABL p210 levels done in the same lab with less than ½ log reduction of BCR-ABL (BA) 3-6 months apart.
- ECOG PS of ≤ 3
Adequate organ function, as defined by the following:
ANC ≥ 500 cells/mm3 Platelet count ≥ 50,000 cells/mm3 Serum bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN Alkaline phosphatase ≤ 2.5 x ULN
- WOCP as defined as defined as not surgically sterile or not one year post-menopausal, must have a negative result for a serum or urine pregnancy test within 7 days of initial receipt of study drug. Surgically sterile is defined as having had a hysterectomy, tubal ligation, or oophorectomy.
- WOCP must use a medically accepted method of contraception and must agree to continued use of this method for the duration of the study and for 30 days after last dose of study drug. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD) known to have a failure rate of less than 1% per year, or steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method.
- Male subjects capable of producing offspring, must use a medically accepted method of birth control and agree to continued use of this method for the duration of the study and for 30 days after last dose of study drug because of the possible effects on spermatogenesis. Acceptable methods of contraception include abstinence, barrier method with spermicide, WOCP partner's use of an IUD known to have a failure rate of less than 1% per year, WOCP partner's use of steroidal contraceptive (oral, implanted or injected) in conjunction with a barrier method, WOCP partner is surgically sterile or 1 year postmenopausal. In addition, male subjects may not donate sperm for the duration of the study and for 30 days after last dose of study drug.
Exclusion Criteria:
- Has a malignancy or infection requiring active treatment
- Has a known HIV infection, Hepatitis B , or Hepatitis C infection
- Has a known symptomatic congestive heart failure (CHF), unstable angina or cardiac arrhythmia
- Is using Aspirin or NSAID or COX-I
- Is known to be non-compliant to medications.
- Has, in the opinion of the physician investigator, an uncontrolled medical or psychiatric disorder.
- Has active central nervous system (CNS) leukemia.
- Is preceding allogeneic stem HSCT.
- Has a known T 315 I mutation.
- Is taking FISH oil at EPA dose > 500 mg
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Eicosapentaenoic Acid (EPA)
Phase I: TKI with escalating/de-escalating doses of EPA to determine MTD. Phase I dose levels: Dose Level 1 = EPA 1500 mg orally once per day; Dose Level 2 = EPA 2000 mg orally once per day; Dose Level 3 = EPA 3000 mg orally once per day; Dose Level -1 = EPA 1000 mg orally once per day; Dose Level -2 = EPA 500 mg orally once per day. Phase II: TKI administered in combination with the recommended Phase II dose of EPA |
Eicosapentaenoic Acid once per day orally
Other Names:
Tyrosine kinase inhibitor to be administered at subjects' pre-study dose
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I - Recommended Phase II Dose of EPA
Time Frame: the time of initiation of the study medication to 30 days after last dose of study medication
|
Recommended Phase II dose of EPA will be established by using a standard 3 + 3 statistical design to determine the MTD as assessed by DLTs when administered orally in combination with a TKI in subjects with CML in stable chronic phase.
Toxicity will be evaluated using the NCI Common Toxicity Criteria (CTC) version 5.0.
|
the time of initiation of the study medication to 30 days after last dose of study medication
|
Phase II - Anti-CML Response to Recommended Phase II Dose Eicosapentaenoic Acid
Time Frame: 1 year
|
BCR-ABL transcript levels will be assessed every 3 months post initiation of Eicosapentaenoic Acid to assess Anti-CML response.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Molecular Responses of CML
Time Frame: 1 year
|
Log reduction from stable molecular response with bcr-abl PCR at MR 3 or more to bcr-abl to major molecular response (MR 4.5) or complete molecular response
|
1 year
|
Induction of Apoptosis in CML Leukemia Stem Cell by Formation of Δ12-PGJ3 and Other Metabolites
Time Frame: 2 years
|
Apoptosis will be analyzed by in vitro correlative studies using subject's plasma with effect on known leukemia cell line with CML leukemic stem cells.
EPA metabolite will be examined by flow cytometry using Annexin V staining and adding serum from treated study subject to murine CML cells grown in vitro culture.
The evaluation will be done at baseline, Month 1, and every 3 months up to year 2
|
2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Seema Naik, MD, Penn State Cancer Institute
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 (Actual)
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
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Dasatinib
Other Study ID Numbers
- 17-085
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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 Chronic Myeloid Leukemia, Chronic Phase
-
Asan Medical CenterTerminatedLeukemia, Chronic Myeloid | Myeloid Leukemia, Chronic, Chronic Phase | Myeloid Leukemia, Chronic, Accelerated PhaseKorea, Republic of
-
Newcastle UniversityBristol-Myers Squibb; Institute of Cancer Research, United Kingdom; Newcastle-upon-Tyne... and other collaboratorsCompletedMyeloid Leukemia, Chronic, Chronic PhaseUnited Kingdom
-
ChemGenex PharmaceuticalsTerminatedMyeloid Leukemia, Chronic, Chronic-Phase | Myeloid Leukemia, Chronic | Myeloid Leukemia, Chronic, Accelerated-Phase | Blast PhaseUnited States
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.CompletedChronic Myelogenous Leukemia - Chronic PhaseChina
-
Fundacion Espanola para la Curacion de la Leucemia...Pfizer; Roche Farma, S.ATerminatedChronic Phase-Chronic Myeloid LeukemiaSpain
-
TakedaActive, not recruitingMyeloid Leukemia, Chronic, Chronic PhaseUnited States, Spain, Taiwan, Australia, Canada, Russian Federation, Sweden, Switzerland, Germany, United Kingdom, Poland, Korea, Republic of, Argentina, Hong Kong, Singapore, Italy, Chile, Czechia, Denmark, France, Portugal
-
H. Lee Moffitt Cancer Center and Research InstituteIncyte Corporation; H. Jean Khoury Cure CML ConsortiumRecruitingChronic Myeloid Leukemia, Chronic Phase | Chronic Phase Chronic Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)TerminatedAccelerated Phase Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
Korean Society of HematologyNot yet recruitingChronic Myeloid Leukemia, Chronic Phase
-
Jiangsu Hansoh Pharmaceutical Co., Ltd.RecruitingCML, Chronic Phase | CML, Accelerated PhaseChina
Clinical Trials on Eicosapentaenoic Acid
-
Samuel FortinTerminated
-
National Institute of Mental Health (NIMH)CompletedBipolar Disorder | Mood Disorder | Involutional DepressionUnited States
-
New York State Psychiatric InstituteWithdrawnBipolar DisorderUnited States
-
National Institute on Alcohol Abuse and Alcoholism...CompletedHealthyUnited States
-
Brigham and Women's HospitalTerminatedCoronary Artery Disease | Type 2 DiabetesUnited States
-
Recep Tayyip Erdogan University Training and Research...Not yet recruitingGestational Diabetes
-
Vanderbilt UniversityCompleted
-
University of WashingtonNational Heart, Lung, and Blood Institute (NHLBI); American Thoracic Society; American Society for Parenteral and Enteral Nutrition and other collaboratorsCompletedAcute Respiratory Distress Syndrome | Acute Lung Injury | Respiratory Distress Syndrome, AdultUnited States, Canada
-
National Institute on Alcohol Abuse and Alcoholism...CompletedObesity | Healthy Subjects | Weight Gain | WomenUnited States