Study of IRX5183 in Relapsed and Refractory Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT02749708|
Recruitment Status : Recruiting
First Posted : April 25, 2016
Last Update Posted : March 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML)||Drug: IRX5183||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of IRX5183 in Relapsed and Refractory Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)|
|Study Start Date :||April 2016|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2021|
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.
In the phase II part of the study, the investigators will use the optimal dose identified in phase I and will aim to recruit a total of 27 patients per a Simon's 2 stage design. After induction, all patients who do not experience significant toxicity or disease progression will continue on a consolidation/maintenance phase of the study in which 4 additional 28-day cycles of IRX5183 will be administered. This phase will use the same dose used in the induction phase for each individual patient.
- 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.
- Measure trough plasma levels of IRX5183 on day 1 and day 14. [ Time Frame: 4 years ]To determine pharmacokinetic (PK) parameters of IRX5183, we will obtain trough peripheral blood samples during the first cycle of therapy.
- Measure peak plasma/bone marrow levels of IRX5183 on day 1 and day 14. [ Time Frame: 4 years ]To determine PK parameters of IRX5183, we will obtain peak peripheral blood/bone marrow samples during the first cycle of therapy.
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02749708
|Contact: B. Douglas Smith, MDfirstname.lastname@example.org|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: B. Douglas Smith, MD 410-614-5048 email@example.com|