Chronic Myeloid Leukemia, Chronic PhasePhase 1/2NCT04006847
Omega -3 Fatty Acid in Combination With Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
A Phase 1/2 study testing Eicosapentaenoic Acid and Tyrosine kinase inhibitor in people with Chronic Myeloid Leukemia, Chronic Phase, run by Milton S. Hershey Medical Center at 1 site in United States.
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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia, Chronic Phase
- What is being tested?
- Eicosapentaenoic Acid and Tyrosine kinase inhibitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2020to 21 May 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
About this study
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
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.
Read the 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.
- Conditions
- Chronic Myeloid Leukemia, Chronic Phase
- Being tested
- Eicosapentaenoic Acid, Tyrosine kinase inhibitor
- Keywords
- Omega-3 Fatty Acid, Eicosapentaenoic Acid, Tyrosine Kinase Inhibitors, TKI, GoldAID Eicosapentaenoic Acid, Fish Oil
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eicosapentaenoic AcidDrug
Also called Omega-3 fatty acid
Eicosapentaenoic Acid once per day orally
Tyrosine kinase inhibitorDrug
Also called TKI, Imatinib, Dasatinib, Nilotinib
Tyrosine kinase inhibitor to be administered at subjects' pre-study dose
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Eicosapentaenoic Acid; Drug: Tyrosine kinase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 1 year
Secondary outcomes (2)
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
Measured: 1 year
Induction of Apoptosis in CML Leukemia Stem Cell by Formation of Δ12-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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start14 Sep 2020
- Primary completion21 May 2021
- Study completion21 May 2021
Why it stopped: Product complaint
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Myeloid Leukemia, Chronic PhaseStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Seema Naik, MD, Milton S. Hershey Medical Center
- Investigators
- Seema Naik, MD, Principal investigator, Penn State Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04006847
- Sponsor's protocol ID
- 17-085
- Status last verified
- Jun 2022
- First submitted
- 2 Jul 2019
- Last updated
- 1 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04006847
- Acronym / sponsor ID
- 17-085
- Conditions
- Chronic Myeloid Leukemia, Chronic Phase
- Keywords
- Omega-3 Fatty Acid, Eicosapentaenoic Acid, Tyrosine Kinase Inhibitors, TKI, GoldAID Eicosapentaenoic Acid, Fish Oil
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Product complaint
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 21 May 2021 (actual)
- Study completion
- 21 May 2021 (actual)
- First posted
- 5 Jul 2019 (actual)
- Results
- Posted 1 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Eicosapentaenoic Acid (EPA) | Experimental | Drug: Eicosapentaenoic Acid, Drug: Tyrosine kinase inhibitorPhase 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eicosapentaenoic AcidAlso: Omega-3 fatty acidEicosapentaenoic Acid once per day orally | Drug | Eicosapentaenoic Acid (EPA) |
| Tyrosine kinase inhibitorAlso: TKI, Imatinib, Dasatinib, NilotinibTyrosine kinase inhibitor to be administered at subjects' pre-study dose | Drug | Eicosapentaenoic Acid (EPA) |
Primary outcome
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.
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.
2 secondary outcomes
Molecular Responses of CML
Time frame: 1 year
Induction of Apoptosis in CML Leukemia Stem Cell by Formation of Δ12-PGJ3 and Other Metabolites
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seema Naik, MD principal investigator
Penn State Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Eicosapentaenoic Acid and Tyrosine kinase inhibitor in people with Chronic Myeloid Leukemia, Chronic Phase, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2022.