Phase 1/2 Study of Enasidenib (AG-221) in Adults With Advanced Hematologic Malignancies With an Iā¦ (NCT01915498) | Clinical Trial Compass
CompletedPhase 1/2
Phase 1/2 Study of Enasidenib (AG-221) in Adults With Advanced Hematologic Malignancies With an Isocitrate Dehydrogenase Isoform 2 (IDH2) Mutation
United States345 participantsStarted 2013-08-27
Plain-language summary
The primary objectives of Phase 1 Dose Escalation/Part 1 Expansion are:
* To assess the safety and tolerability of treatment with enasidenib administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle in participants with advanced hematologic malignancies.
* To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of enasidenib in participants with advanced hematologic malignancies.
The primary objective of Phase 2 is:
ā¢ To assess the efficacy of enasidenib as treatment for participants with relapsed or refractory (R/R) acute myelogenous leukemia (AML) with an IDH2 mutation.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
ā. Subject must be greater than or equal to 18 years of age.
ā. Subjects must have an advanced hematologic malignancy including:
ā. Diagnosis of acute myelogenous leukemia (AML) according to World Health Organization (WHO) criteria;
ā. Diagnosis of Myelodysplastic syndrome (MDS) according to WHO classification with refractory anemia with excess blasts (RAEB-1 or RAEB-2), or considered high-risk by the Revised International Prognostic Scoring System (IPSS-R), that is recurrent or refractory, or the subject is intolerant to established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit), according to the treating physician and with approval of the Medical Monitor.
ā. Subjects must have documented IDH2 gene-mutated disease:
ā. Subjects must be amenable to serial bone marrow sampling, peripheral blood sampling and urine sampling during the study.
ā. Subjects must be able to understand and willing to sign an informed consent. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or sites Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
What they're measuring
1
Phase 1 Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLT)
Timeframe: From time of first dose up to the end of Cycle 1; 28 days
2
Phase 1 Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timeframe: From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff date of 01 September 2017; median treatment duration in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months).
3
Phase 1 Dose Expansion: Number of Participants With Treatment Emergent Adverse Events
Timeframe: From the first dose of investigational product (IP) up to 28 days after the last dose of IP up to the data cutoff date of 01 September 2017; median treatment duration in Part 1 Expansion was 5.2 months (range 0.5 to 32.8 months).
Timeframe: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
5
Phase 2 Dose Expansion: Number of Participants With Treatment Emergent Adverse Events
Timeframe: From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff of date of 01 September 2017; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
. Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 2.
Exclusion criteria
ā. Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-221, or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post GVHD and/or topical steroids for ongoing skin GVHD is permitted with Medical Monitor approval.)
ā. Subjects who received systemic anticancer therapy or radiotherapy \< 14 days prior to their first day of study drug administration. (Hydroxyurea is allowed for up to 28 days after the start of AG-221 for the control of peripheral leukemic blasts in subjects with white blood cell \[WBC\] counts \> 30,000/Ī¼L as well as prior to enrollment).
ā. Subjects who received a small molecule investigational agent \< 14 days prior to their first day of study drug administration. In addition, the first dose of AG-221 should not occur before a period ā„ 5 half-lives of the investigational agent has elapsed.
ā. Subjects taking the following sensitive cytochrome P450 (CYP) substrate medications that have a narrow therapeutic range are excluded from the study unless they can be transferred to other medications within ā„5 half-lives prior to dosing: paclitaxel (CYP2C8) warfarin, phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline and tizanidine (CYP1A2).
ā. Subjects taking the P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) transporter-sensitive substrates digoxin and rosuvastatin should be excluded from the study unless they can be transferred to other medications within ā„ 5 half-lives prior to dosing.
ā. Subjects for whom potentially curative anticancer therapy is available.
ā. Subjects who are pregnant or lactating.
ā. Subjects with an active severe infection that required anti-infective therapy or with an unexplained fever \> 38.5Ā°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled).
Safety Follow-up: Number of Participants With Treatment Emergent Adverse Events
Timeframe: From the primary analysis cut-off date of 01 September 2017 to the final analysis cut-off date of 29 July 2019, a maximum of 23 months.