Description:
This is a Phase I/II single site, open label clinical trial. The purpose of the Phase I
portion is to determine the safety, tolerability, and recommended Phase II dose of
Eicosapentaenoic Acid (EPA) when given daily in combination with a Tyrosine Kinase Inhibitor
(TKI) in subjects with Chronic Myeloid Leukemia (CML) in chronic stable phase. The
recommended Phase II dose will be the maximum tolerated dose (MTD) of EPA as determined by
the evaluation of dose-limiting toxicities (DLTs). The Phase II portion will subsequently
examine the Anti-CML effects of EPA when administered with a TKI at the recommended Phase II
dose. This efficacy objective will be done by evaluating BCR-ABL p210 quantitative PCR blood
levels every 3 months to 1 year.
Title
- Brief Title: Omega -3 Fatty Acid in Combination With Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
17-085
- NCT ID:
NCT04006847
Conditions
- Chronic Myeloid Leukemia, Chronic Phase
Interventions
Drug | Synonyms | Arms |
---|
Eicosapentaenoic Acid | Omega-3 fatty acid | Eicosapentaenoic Acid (EPA) |
Tyrosine kinase inhibitor | TKI, Imatinib, Dasatinib, Nilotinib, Bosutinib | Eicosapentaenoic Acid (EPA) |
Purpose
This is a Phase I/II single site, open label clinical trial. The purpose of the Phase I
portion is to determine the safety, tolerability, and recommended Phase II dose of
Eicosapentaenoic Acid (EPA) when given in combination with a Tyrosine Kinase Inhibitor (TKI)
in subjects with Chronic Myeloid Leukemia (CML) in chronic stable phase. The recommended
Phase II dose will be the maximum tolerated dose (MTD) of EPA as determined by the evaluation
of dose-limiting toxicities (DLTs). The Phase II portion will subsequently examine the
Anti-CML effects of EPA when administered with a TKI at the recommended Phase II dose. This
efficacy objective will be done by evaluating BCR-ABL p210 quantitative PCR blood levels
every 3 months to 1 year.
Detailed Description
Targeting CML leukemia stem cells is of paramount importance in successfully preventing
cancer relapse. EPA metabolite, Δ12-PGJ3 may represent a new chemotherapeutic agent for
leukemia that targets leukemia stem cells. Selective targeting of cancer stem cells may be
potentially a highly effective treatment for cancer. As most CML patients treated with a TKI
will reach a complete cytogenetic response, quantification of residual BCR-ABL transcripts by
quantitative reverse transcription PCR (RT-qPCR) is a critical tool to further monitor
response kinetics. Addition of EPA to TKI may help decrease residual BCR-ABL positive (Ph+)
leukemia stem cells.
Trial Arms
Name | Type | Description | Interventions |
---|
Eicosapentaenoic Acid (EPA) | Experimental | Phase I: TKI with escalating/de-escalating doses of EPA to determine MTD.
Phase I dose levels: Dose Level 1 = EPA 1500 mg orally; Dose Level 2 = EPA 2000 mg orally; Dose Level 3 = EPA 3000 mg orally; Dose Level -1 = EPA 1000 mg orally; Dose Level -2 = EPA 500 mg orally.
Phase II: TKI administered in combination with the recommended Phase II dose of EPA | - Eicosapentaenoic Acid
- Tyrosine kinase inhibitor
|
Eligibility Criteria
Inclusion Criteria:
Male or female at least 18 years of age.
Confirmed diagnosis of CML
Is at least 18 months from CML diagnosis.
Current concomitant treatment with TKI therapy (Imatinib, Dasatinib, Nilotinib or
Bosutinib; excluding Ponatinib).
One of the following confirmed:
1. break point cluster ( BCR)-ABL Polymerase chain reaction (PCR) at stable molecular
disease (e.g., Major Molecular Response (MMR) stable but not Complete Molecular
Response (CMR) or;
2. HR but no MMR.
Stable molecular response defined as 2 sequential BCR-ABL levels done in the same lab with
less than one-half log reduction of BCR-ABL (BA)
Eastern Cooperative Oncology Group (ECOG) Performance Score of less than 3
Absolute neutrophil count greater than or equal to 500 cells/mm^3
Platelet count greater than or equal to 50,000 cells/mm^3
Serum bilirubin less than or equal to 1.5 times the upper limit of normal
Alanine transaminase (ALT) and Aspartate transaminase (AST) less than or equal to 2.5 times
the upper limit of normal
Alkaline phosphatase less than or equal to 2.5 times the upper limit of normal
Not pregnant. Females of child bearing potential 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.
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
Exclusion Criteria:
Known additional malignancy requiring active treatment
Active infection requiring antibiotic treatment.
Known i.e. previously documented HIV, Hepatitis B, or Hepatitis C infection.
Known symptomatic congestive heart failure, unstable angina or cardiac arrhythmia.
Current concomitant use of non NSAIDs (including Aspirin) or cyclooxygenase-1 (COX-1); a
washout period of 4 weeks prior to enrollment is permitted.
Known non-compliance with medications.
In the opinion of a PI or Sub-I, an uncontrolled medical or psychiatric disorder.
Active central nervous system leukemia.
Preceding allogeneic stem hematopoietic stem cell transplant.
Known T315I mutation.
Current concomitant use of fish oil at EPA dose greater than 500 mg; a washout period of 4
weeks prior to enrollment is permitted.
Known hypersensitivity to EPA.
Pregnant or breastfeeding
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase I - Recommended Phase II dose of EPA |
Time Frame: | 1 month |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Number of subjects who experience treatment related Adverse Events (AEs) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Using the NCI CTC Version 5.0, AEs will be assessed from the time of initiation of investigational medication |
Measure: | Severity of AEs experienced by study subjects |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Using the NCI CTC Version 5.0, the highest grade of all treatment related AEs collected will be used to determine severity |
Measure: | Study subject compliance with investigational regimen |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Proportion of protocol prescribed doses taken by subjects |
Measure: | Molecular responses of CML |
Time Frame: | 1 year |
Safety Issue: | |
Description: | 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 |
Measure: | Induction of apoptosis in CML leukemia stem cell by formation of Δ12-PGJ3 and other metabolites |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Analyzed by in vitro correlative studies using subject's plasma with effect on known leukemia cell line with CML leukemic stem cells. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Milton S. Hershey Medical Center |
Trial Keywords
- Omega-3 Fatty Acid
- Eicosapentaenoic Acid
- Tyrosine Kinase Inhibitors
- TKI
- GoldAID Eicosapentaenoic Acid
- Fish Oil
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