IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03515512|
Recruitment Status : Recruiting
First Posted : May 3, 2018
Last Update Posted : June 13, 2019
This research study is studying a targeted therapy drug as a possible treatment for IDH2 mutant acute myeloid leukemia or chronic myelomonocytic leukemia while undergoing hematopoietic stem cell transplantation.
The drug involved in this study is:
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia||Drug: Enasidenib||Phase 1|
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has approved enasidenib as a treatment option for some cancers, but not for the specific indication under study with this protocol.
Enasidenib is currently used to treat AML with an IDH2 mutation that has come back or has not improved after previous AML treatment. This study is examining whether or not enasidenib may be beneficial and well-tolerated as an agent to prevent the relapse of IDH2-mutated AML or other myeloid neoplasms after participants have undergone hematopoietic stem cell transplantation (HSCT). IDH2 is an enzyme that, when mutated, can overproduce metabolites and compounds that contribute to the growth of tumors and cancerous cells. Enasidenib may help block the over production of these substances.
There is an FDA-approved test available to detect IDH2 mutations in patients with AML, but for the purposes of participation in this clinical trial, an investigational test may be used to determine the presence of an IDH2 mutation.
In this research study, the investigators are:
- Looking for the maximum dose of enasidenib that individuals can take without experiencing severe side effects following HSCT.
- Looking at how often Graft-Versus-Host-Disease (GVHD) occurs in participants taking enasidenib. GVHD is a complication of transplant.
- Assessing the rates of relapse for participants taking enasidenib after HSCT.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation|
|Actual Study Start Date :||July 17, 2018|
|Estimated Primary Completion Date :||May 31, 2021|
|Estimated Study Completion Date :||May 31, 2024|
Enasidenib will be administered orally once daily in 28-day cycles
Enasidenib may help block the over production of IDH2, which when mutated, can overproduce metabolites and compounds that contribute to the growth of tumors and cancerous cells
Other Name: idhifa
- Maximum Tolerated Dose (MTD) [ Time Frame: 28 Days ]The maximum tolerated dose of Enasidenib in this patient population. The Maximum Tolerated Dose (MTD) is defined as the highest dose level at which 0 or 1 of six patients experiences a dose-limiting toxicity (DLT). MTD is determined using a standard 3 + 3 dose escalation cohort, where 3 participants will be enrolled on the starting dose of 50 mg daily and if no DLT is experienced after a full 28-day cycle, 3 additional participants will be enrolled at the next dose level of 100mg daily. If during any dose level, 1 patient out of 3 develops a DLT, then 3 additional patients will be added to that dose level. If 2 out of the 3 patients placed on any dose level experience a DLT, the preceding dose is considered MTD. If 1 out of 6 participants has a DLT, the next higher dose level will commence accrual. If ≥ 2 of 6 patients have a DLT, then the preceding dose will be considered MTD.
- Number of participants with dose limiting toxicities (DLT) [ Time Frame: 28 days ]Dose limiting toxicities are adverse events that occur during the first 28-day cycle that are considered serious enough to prevent an increase in the Enasidenib dose level. Adverse events are graded and documented per Common Terminology Criteria for Adverse Events (CTCAE 4).
- The number of participants with Enasidenib related adverse events [ Time Frame: From the start of treatment until 30 days after the end of treatment, treatment may continue for up to 12 28-day cycles ]The number of participants with treatment related adverse events grouped by grade. Adverse events are assessed using Common Terminology Criteria for Adverse Events (CTCAE 4). Adverse events are considered to be related to treatment if they are deemed to be possibly, probably, or definitely related to treatment with Enasidenib by the investigator.
- Cumulative incidence of acute GVHD [ Time Frame: Cycle 1 days 1, 8, and 15; day 1 of every subsequent cycle (cycles are 28-days), up to 100 days after the start of treatment ]The cumulative incidence of acute graft versus host disease (GVHD). Acute GVHD is graded according to a composite grading of the clinical stages of skin rash, liver function, and intestinal tract function. Skin rash is assessed by the portion of the body covered by rash, liver function is assessed based on blood bilirubin levels, and intestinal track function is assessed based on the volume of diarrhea per day. The acute GVHD grade ranges from 1 to 4 with 1 representing less severe effects and 4 the most severe. The incidence represents the proportion of participants that experienced any grade acute GVHD.
- Cumulative incidence of chronic GVHD [ Time Frame: Cycle 1 days 1, 8, and 15; Day 1 of cycles 2-12 (1 cycle is 28-days), up to 1 year of total follow-up ]
Cumulative incidence of chronic graft versus host disease (GVHD). cGHVD is assessed as per the National Institutes of Health consensus development project on criteria for clinical trials in cGVHD. cGVHD is graded as mild, moderate, or severe. The cGVHD grade is based on an aggregate score of different organ systems. The organ systems are graded from 0 to 3, with 0 being no-symptoms and 3 being the most severe symptoms. The cumulative incidence represents the proportion of participants that have any grade cGVHD.
- Mild: Involves only 1 or 2 organs or sites (except the lung), with no clinically significant functional impairment
- Moderate: Involves at least 1 organ or site with clinically significant but no major disability or 3 or more organs or sites with no clinically significant functional impairment. A lung score of 1 will also be considered moderate cGVHD
- Severe: Indicates major disability caused by cGVHD. A lung score of 2 will also be considered severe cGVHD
- Plasma and marrow 2-hydroxyglutarate levels [ Time Frame: Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up ]Summary of the median 2-hydroxyglutarate levels at each time-point.
- IDH clonal evolution via whole genome sequencing [ Time Frame: Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up ]Count summary of the specific Isocitrate dehydrogenase (IDH) mutations experienced by participants as assessed using whole genome sequencing.
- IDH Mutational burden via next-generation sequencing [ Time Frame: Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up ]Summary of the number of mutations in the Isocitrate dehydrogenase (IDH) gene as assessed using next-generation sequencing.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03515512
|Contact: Amir T Fathi, MDemail@example.com|
|United States, Maryland|
|Johns Hopkins Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Mark Levis, MD firstname.lastname@example.org|
|Principal Investigator: Mark Levis, MD|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02214|
|Contact: Amir T Fathi, MD 617-724-1124 email@example.com|
|Principal Investigator: Amir T Fathi, MD|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Robert j Soiffer, MD RSOIFFER@PARTNERS.ORG|
|Principal Investigator: Robert J. Soiffer, MD|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Alice Mims, MD Alice.Mims@osumc.edu|
|Principal Investigator: Alice Mims, MD|
|Principal Investigator:||Amir t Fathi, MD||Massachusetts General Hospital|