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

NCT04006847 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 17-085
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Myeloid Leukemia, Chronic Phase

Keywords

Omega-3 Fatty Acid; Eicosapentaenoic Acid; Tyrosine Kinase Inhibitors; TKI; GoldAID Eicosapentaenoic Acid; Fish Oil

Outcome Measures

Primary Outcomes (2)

• Phase I - Recommended Phase II Dose of EPA

  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

  BCR-ABL transcript levels will be assessed every 3 months post initiation of Eicosapentaenoic Acid to assess Anti-CML response.

  1 year

Secondary Outcomes (2)

• Molecular Responses of CML

  1 year

• Induction of Apoptosis in CML Leukemia Stem Cell by Formation of Δ12-PGJ3 and Other Metabolites

  2 years

Study Arms (1)

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 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

Drug: Eicosapentaenoic Acid; Drug: Tyrosine kinase inhibitor

Interventions

Eicosapentaenoic Acid DRUG

Eicosapentaenoic Acid once per day orally

Also known as: Omega-3 fatty acid

Eicosapentaenoic Acid (EPA)

Tyrosine kinase inhibitor DRUG

Tyrosine kinase inhibitor to be administered at subjects' pre-study dose

Also known as: TKI, Imatinib, Dasatinib, Nilotinib, Bosutinib

Eicosapentaenoic Acid (EPA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

Eicosapentaenoic Acid; Fatty Acids, Omega-3; Tyrosine Kinase Inhibitors; Imatinib Mesylate; Dasatinib; nilotinib; bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Limitations and Caveats

Due to the product issues, the trials was halted.

Results Point of Contact

• Title: Seema Naik, MD
• Organization: Penn State Health

snaik@pennstatehealth.psu.edu

7175318678

Study Officials

• Seema Naik, MD

  Penn State Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Cancer Institutue

Model Details: Phase I/II, open-label, single site study using a standard 3 + 3 statistical design to determine the MTD and the recommended Phase 2 dose for oral EPA when administered to subjects receiving on a TKI pre-study.

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 5, 2019
• Study Start: September 14, 2020
• Primary Completion: May 21, 2021
• Study Completion: May 21, 2021
• Last Updated: July 1, 2022
• Results First Posted: July 1, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)