Clinical Trials /

Omega -3 Fatty Acid in Combination With Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

NCT04006847

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.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Eicosapentaenoic AcidOmega-3 fatty acidEicosapentaenoic Acid (EPA)
Tyrosine kinase inhibitorTKI, Imatinib, Dasatinib, Nilotinib, BosutinibEicosapentaenoic 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

NameTypeDescriptionInterventions
Eicosapentaenoic Acid (EPA)ExperimentalPhase 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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