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

Chronic Myeloid Leukemia, Chronic Phase Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT04006847
• Other study ID #: 17-085
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 14, 2020
• Est. completion date: May 21, 2021

Study information

• Verified date: June 2022
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: May 21, 2021
• Est. primary completion date: May 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female =18 years of age.

2. Confirmed diagnosis of CML = 18 months from diagnosis.

3. 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.

4. One of the following confirmed:

1. BCR-ABL p210 at stable molecular disease (e.g., MMR stable but not CMR)

2. HR but no MMR.

5. 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.

6. ECOG PS of = 3

7. 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

8. 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.

9. 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.

10. 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:

1. Has a malignancy or infection requiring active treatment

2. Has a known HIV infection, Hepatitis B , or Hepatitis C infection

3. Has a known symptomatic congestive heart failure (CHF), unstable angina or cardiac arrhythmia

4. Is using Aspirin or NSAID or COX-I

5. Is known to be non-compliant to medications.

6. Has, in the opinion of the physician investigator, an uncontrolled medical or psychiatric disorder.

7. Has active central nervous system (CNS) leukemia.

8. Is preceding allogeneic stem HSCT.

9. Has a known T 315 I mutation.

10. Is taking FISH oil at EPA dose > 500 mg

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia, Chronic Phase
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Eicosapentaenoic Acid
Eicosapentaenoic Acid once per day orally
• Tyrosine kinase inhibitor
Tyrosine kinase inhibitor to be administered at subjects' pre-study dose

Locations

Country	Name	City	State
United States	Penn State Cancer Institute	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Molecular Responses of CML	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
Secondary	Induction of Apoptosis in CML Leukemia Stem Cell by Formation of ?12-PGJ3 and Other Metabolites	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