Acute Myeloid Leukemia (AML)Phase 1NCT02749708
Study of IRX5183 in Relapsed and Refractory Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome
A Phase 1 study testing IRX5183 in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the use of IRX5183 in 1) patients with relapsed and/or refractory AML and 2) patients with high-risk MDS or chronic myelomonocytic leukemia (CMML). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)
- What is being tested?
- IRX5183
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jan 2017to 14 Aug 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be able to understand and voluntarily sign an informed consent form.
- Age ≥ 18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Pathologically confirmed disease with A or B as follows:
- AML patients who either have:
- Relapsed or refractory disease after receiving one or more courses of induction chemotherapy, hypomethylating agent therapy, or bone marrow transplant or
Show all 20Show fewer
- de novo AML but not deemed to be a candidate for conventional therapy based on age, co-morbidities, or patient preference
- MDS, CMML, or MDS/myeloproliferative neoplasm (MPN) with high risk features as defined below who have relapsed after initial response or are refractory (failure to achieve a complete remission (CR), partial remission (PR), or hematologic improvement (HI)) after receiving at least 4 cycles of hypomethylating agents 5-azacitidine or decitabine ± other therapies ± bone marrow transplant OR with de novo MDS but have refused to receive hypomethylating therapy:
- Intermediate (INT)-2 or high International Prognostic Scoring System (IPSS) score OR high or very high revised IPSS (IPSS-R) or
- Secondary MDS (defined as MDS developing in a patient with an antecedent hematologic disorder or any patient with prior chemotherapy or radiation exposure) or
- INT-1 IPSS or intermediate IPSS-R MDS with excess blasts (≥5% blasts in bone marrow) or transfusion-dependency or
- MDS progressing to oligoblastic AML with 21-30% bone marrow blasts or
- CMML or MDS/MPN with ≥ 5% marrow blasts, transfusion-dependency, abnormal karyotype, or proliferative features (white blood cell count ≥13,000/µL, splenomegaly on physical examination, or extramedullary disease)
- Eastern Cooperative Oncology Group performance status of ≤ 2 at study entry or Karnofsky > 60%.
- Laboratory test results within these ranges:
- Creatinine level of 3 mg/dL or lower, total bilirubin ≤ 3 mg/dL unless due to Gilbert's syndrome, hemolysis, or ineffective hematopoiesis, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal, white blood count (WBC) ≤ 10,000/µL
- Patients must not have received any other treatment for their disease, including hematopoietic growth factors, aside from hydroxyurea for count control, within three weeks of beginning the trial, and should have recovered from all toxicities of prior therapy (to grade 0 or 1).
- Patients requiring hydroxyurea to bring WBC below 10,000/µL prior to study enrollment will require a 48-hour washout prior to starting the study drug.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to start of IRX5183.
- Patients must have no clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
Who cannot join
- Any serious medical condition or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, laboratory abnormality, or psychiatric illness/social situations that would limit compliance with study requirements or prevent the subject from signing the informed consent form.
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 21 days of baseline.
- Known hypersensitivity or history of allergic reactions attributed to compounds of similar chemical or biologic composition to IRX5183.
- Prior use of other retinoid therapies in the 3 months prior to enrollment in the study.
- Patients with other active cancers receiving anti-cancer agents, with exceptions being hormonal therapy for breast or prostate cancer and skin cancers treated with local therapies only.
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (e.g. alopecia, hypothyroid, neuropathy, etc.).
- Pregnant women are excluded from this study because of potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IRX5183, breastfeeding should be discontinued if the mother is treated with IRX5183.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: Phase I/II Study of IRX5183 in Relapsed and Refractory Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
The purpose of this study is to evaluate the use of IRX5183 in 1) patients with relapsed and/or refractory AML and 2) patients with high-risk MDS or chronic myelomonocytic leukemia (CMML).
Read the detailed description
This research is being done to learn about the safety and effectiveness of an investigational drug, IRX5183, in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). IRX5183 is a derivative of Vitamin A. IRX5183 is a drug that is designed to cause cancer cells to mature and then die. It is thought that it will stop the uncontrolled growth of leukemia cells.
These are 2 parts to this study. The purpose of the first part is to test the safety of IRX5183 at different dose levels. The investigators want to find out what effects, good and/or bad, it has on AML or MDS. Once the investigators figure out the best and safest dose of IRX5183, the investigators will enter the second part of the study using this dose. The purpose of the second part is to see if IRX5183 is effective as a treatment for AML or MDS. To date, IRX5183 has been used in about 25 people.
The first part of the study is called a "Phase I" study. Phase I studies use drugs starting at low doses and slowly increase the amounts of the study drugs that are given to people until the side effects of the drugs are too high to give more. This means that not all people in the study will get the same dose of IRX5183. Doses at the beginning of the study will be lower than doses at the end of the study. Because of the design of the study, some people may get doses that are too low to have an effect, and other people will probably get doses that cause side effects.
People with AML, MDS, or CMML that has 1) not responded to standard therapy or 2) has returned after a previous response may join.
- Conditions
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)
- Being tested
- IRX5183
- Keywords
- IRX5183, relapsed/refractory AML, high-risk MDS
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IRX5183Drug
IRX5183 will be administered orally daily on days 1-28 of each cycle for 2 cycles of induction. In the phase I part of the study, there will be 3 dose levels (dose level 1 [DL1] with 50 mg, DL2 with 75 mg, and DL3 with 100 mg), with 1 additional dose level to be only used if excessive toxicity noted at the DL1. There will be no intra-patient dose escalation. A phase II portion of the study was originally planned, but the study was terminated prior to phase II enrollment.
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1 | Experimental | IRX5183 50 mg daily Receives: Drug: IRX5183 |
| Dose level 2 | Experimental | IRX5183 75 mg daily Receives: Drug: IRX5183 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate safety and tolerability of IRX5183 in phase I using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0, to determine dose limiting toxicities (DLTs) and the recommended phase 2 dose (RP2D).
We will determine DLTs at specified dose levels to determine the RP2D.
Measured: 2 years
Determine the best overall response rate (ORR) per International Working Group (IWG) criteria with the RP2D after at least 2 therapy cycles.
The primary endpoint of phase II is best ORR per IWG criteria after at least 2 cycles of therapy. If enough patients achieve an objective response, enrollment will continue to a second stage, per a Simon's 2 stage design.
Measured: 2 years
Secondary outcomes (9)
Measure trough plasma levels of IRX5183 on day 1 and day 14.
To determine pharmacokinetic (PK) parameters of IRX5183, we will obtain trough peripheral blood samples during the first cycle of therapy.
Measured: 4 years
Measure peak plasma/bone marrow levels of IRX5183 on day 1 and day 14.
To determine PK parameters of IRX5183, we will obtain peak peripheral blood/bone marrow samples during the first cycle of therapy.
Measured: 4 years
Determine flow markers of differentiation in the peripheral blood and/or bone marrow.
Measured: 4 years
Determine changes in cytogenetics in the peripheral blood and bone marrow before and after treatment with IRX5183.
Measured: 4 years
Determine the time to first and best response, per IWG criteria.
Measured: 4 years
Determine changes in transfusion requirements following therapy with IRX5183.
Measured: 4 years
Assess quality of life with the Functional Assessment of Cancer Therapy-leukemia (FACT-leu) questionnaire at baseline, after 2 cycles, and after 6 cycles of therapy.
Measured: 4 years
Determine event-free survival (EFS) for patients treated with IRX5183.
Measured: 4 years
Determine overall survival (OS) for patients treated with IRX5183.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2016 (estimated)
- Study start30 Jan 2017
- Primary completion14 Aug 2018
- Study completion14 Aug 2018
Why it stopped: Study drug supply expired and could not be renewed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Io Therapeutics
- Responsible party
- Sponsor
- Investigators
- Douglas Smith, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02749708
- Sponsor's protocol ID
- J15219
- Other IDs
- IRB00083855
- Status last verified
- Apr 2019
- First submitted
- 5 Apr 2016
- Last updated
- 22 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ambinder AJ, Norsworthy K, Hernandez D, Palau L, Paun B, Duffield A, Chandraratna R, Sanders M, Varadhan R, Jones RJ, Douglas Smith B, Ghiaur G. A Phase 1 Study of IRX195183, a RARalpha-Selective CYP26 Resistant Retinoid, in Patients With Relapsed or Refractory AML. Front Oncol. 2020 Oct 23;10:587062. doi: 10.3389/fonc.2020.587062. eCollection 2020.
PubMed 33194741
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of IRX5183 in Relapsed and Refractory Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT02749708
- Acronym / sponsor ID
- J15219
- Conditions
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)
- Keywords
- IRX5183, relapsed/refractory AML, high-risk MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study drug supply expired and could not be renewed.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Io Therapeutics
- Study start
- 30 Jan 2017 (actual)
- Primary completion
- 14 Aug 2018 (actual)
- Study completion
- 14 Aug 2018 (actual)
- First posted
- 25 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the use of IRX5183 in 1) patients with relapsed and/or refractory AML and 2) patients with high-risk MDS or chronic myelomonocytic leukemia (CMML).
Detailed description
This research is being done to learn about the safety and effectiveness of an investigational drug, IRX5183, in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). IRX5183 is a derivative of Vitamin A. IRX5183 is a drug that is designed to cause cancer cells to mature and then die. It is thought that it will stop the uncontrolled growth of leukemia cells.
These are 2 parts to this study. The purpose of the first part is to test the safety of IRX5183 at different dose levels. The investigators want to find out what effects, good and/or bad, it has on AML or MDS. Once the investigators figure out the best and safest dose of IRX5183, the investigators will enter the second part of the study using this dose. The purpose of the second part is to see if IRX5183 is effective as a treatment for AML or MDS. To date, IRX5183 has been used in about 25 people.
The first part of the study is called a "Phase I" study. Phase I studies use drugs starting at low doses and slowly increase the amounts of the study drugs that are given to people until the side effects of the drugs are too high to give more. This means that not all people in the study will get the same dose of IRX5183. Doses at the beginning of the study will be lower than doses at the end of the study. Because of the design of the study, some people may get doses that are too low to have an effect, and other people will probably get doses that cause side effects.
People with AML, MDS, or CMML that has 1) not responded to standard therapy or 2) has returned after a previous response may join.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 | Experimental | Drug: IRX5183IRX5183 50 mg daily |
| Dose level 2 | Experimental | Drug: IRX5183IRX5183 75 mg daily |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients must be able to understand and voluntarily sign an informed consent form.
- Age ≥ 18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Pathologically confirmed disease with A or B as follows:
- Eastern Cooperative Oncology Group performance status of ≤ 2 at study entry or Karnofsky > 60%.
Key exclusion criteria (8 listed)
- Any serious medical condition or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, laboratory abnormality, or psychiatric illness/social situations that would limit compliance with study requirements or prevent the subject from signing the informed consent form.
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 21 days of baseline.
- Known hypersensitivity or history of allergic reactions attributed to compounds of similar chemical or biologic composition to IRX5183.
- Prior use of other retinoid therapies in the 3 months prior to enrollment in the study.
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 |
|---|---|---|
| IRX5183IRX5183 will be administered orally daily on days 1-28 of each cycle for 2 cycles of induction. In the phase I part of the study, there will be 3 dose levels (dose level 1 [DL1] with 50 mg, DL2 with 75 mg, and DL3 with 100 mg), with 1 additional dose level to be only used if excessive toxicity noted at the DL1. There will be no intra-patient dose escalation. A phase II portion of the study was originally planned, but the study was terminated prior to phase II enrollment. | Drug | Dose level 1, Dose level 2 |
Primary outcome
Evaluate safety and tolerability of IRX5183 in phase I using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0, to determine dose limiting toxicities (DLTs) and the recommended phase 2 dose (RP2D).
Time frame: 2 years
We will determine DLTs at specified dose levels to determine the RP2D.
Determine the best overall response rate (ORR) per International Working Group (IWG) criteria with the RP2D after at least 2 therapy cycles.
Time frame: 2 years
The primary endpoint of phase II is best ORR per IWG criteria after at least 2 cycles of therapy. If enough patients achieve an objective response, enrollment will continue to a second stage, per a Simon's 2 stage design.
9 secondary outcomes
Measure trough plasma levels of IRX5183 on day 1 and day 14.
Time frame: 4 years
Measure peak plasma/bone marrow levels of IRX5183 on day 1 and day 14.
Time frame: 4 years
Determine flow markers of differentiation in the peripheral blood and/or bone marrow.
Time frame: 4 years
Determine changes in cytogenetics in the peripheral blood and bone marrow before and after treatment with IRX5183.
Time frame: 4 years
Determine the time to first and best response, per IWG criteria.
Time frame: 4 years
Determine changes in transfusion requirements following therapy with IRX5183.
Time frame: 4 years
Assess quality of life with the Functional Assessment of Cancer Therapy-leukemia (FACT-leu) questionnaire at baseline, after 2 cycles, and after 6 cycles of therapy.
Time frame: 4 years
Determine event-free survival (EFS) for patients treated with IRX5183.
Time frame: 4 years
Determine overall survival (OS) for patients treated with IRX5183.
Time frame: 4 years
Results and safety
The study was stopped early (reason given: Study drug supply expired and could not be renewed.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2019.
- Derived from this study: PubMed 33194741Ambinder AJ, Norsworthy K, Hernandez D, Palau L, Paun B, Duffield A, Chandraratna R, Sanders M, Varadhan R, Jones RJ, Douglas Smith B, Ghiaur G. A Phase 1 Study of IRX195183, a RARalpha-Selective CYP26 Resistant Retinoid, in Patients With Relapsed or Refractory AML. Front Oncol. 2020 Oct 23;10:587062. doi: 10.3389/fonc.2020.587062. eCollection 2020.
- 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.
Douglas Smith, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IRX5183 in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 20 inclusion and 8 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 22 Apr 2019. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study drug supply expired and could not be renewed.). Results are not available in the source record.
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?
Evaluate safety and tolerability of IRX5183 in phase I using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0, to determine dose limiting toxicities (DLTs) and the recommended phase 2 dose (RP2D). (time frame: 2 years). 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?
On the ClinicalTrials.gov record for NCT02749708, which also lists 1 linked publication.
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 22 Apr 2019.