Trial Title:
A Study of Gilteritinib in Combination with Ivosidenib or Enasidenib in People with Acute Myeloid Leukemia (AML)
NCT ID:
NCT05756777
Condition:
Acute Myeloid Leukemia (AML)
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Ivosidenib
Gilteritinib
Conditions: Keywords:
Gilteritinib
Ivosidenib
Enasidenib
FLT3/IDH1 Mutations
FLT3/IDH2 Mutations
21-174
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Gilteritinib
Description:
Dose level (-1) 80mg, (1) 120mg, (2) 120mg
Arm group label:
gilteritinib + enasidenib (Cohort 2)
Arm group label:
gilteritinib + ivosidenib (Cohort 1)
Intervention type:
Drug
Intervention name:
Ivosidenib
Description:
Dose level (-1) 250mg, (1) 250mg, (2) 500mg
Arm group label:
gilteritinib + ivosidenib (Cohort 1)
Intervention type:
Drug
Intervention name:
Enasidenib
Description:
Dose level (-1) 50mg, (1) 50mg, (2) 100mg
Arm group label:
gilteritinib + enasidenib (Cohort 2)
Summary:
The researchers are doing this study to see if the combination of gilteritinib with
ivosidenib or enasidenib is a safe and effective treatment for people with
relapsed/refractory AML with FLT3/IDH1 or FLT3/IDH2 gene mutations. The researchers will
also look for the highest dose of the combination of gilteritinib with ivosidenib or
enasidenib that causes few or mild side effects. When the highest safe dose is found,
they will test that dose in new groups of participants.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Adult patient is ≥18 years of age at the time of signing the informed consent form
(ICF)
- Patient is willing and able to adhere to the study visit schedule and other protocol
requirements.
- Patient has a confirmed diagnosis of relapsed AML as per World Health Organization
(2016) guidelines. Patients in morphologic remission with the reappearance of MRD
are also eligible to participate OR the patient has refractory AML as defined below:
1. For patients who received intensive induction chemotherapy they must have
persistent AML (defined as overt disease with over 5% myeloblasts) after at
least one cycle of intensive induction OR
2. For patients treated with low intensity therapy, the patient must be refractory
to treatment with a single agent hypomethylating agent (HMA) or low dose
cytarabine (LDAC) (at least two cycles) or an HMA/LDAC in combination with
venetoclax (at least one cycle) or another standard of care therapy (e.g.
gemtuzumab ozogamicin, glasdegib/LDAC).
- Patient has relapsed or refractory AML with dually mutant IDH2/FLT3, IDH1/FLT3 (ITD
or TKD) , or other FLT3 mutation sensitive to gilteritinib.
a. A Patient receiving enasidenib or ivosidenib as a single agent who acquires a
FLT3 mutation during treatment or a patient on single agent gilteritinib who
acquires an IDH2 or IDH1 mutation during treatment is eligible to participate in
this study
- Patient has documentation of FLT3 and IDH1 or IDH2 mutation in bone marrow or blood
at time of relapsed/refractory status confirmed by next-generation sequencing (NGS)
and/or polymerase chain reaction (PCR) or fragment length analysis within the
previous 30 days by a local CLIA approved test.
- Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
- Patient should have adequate renal function, defined as creatine clearance ≥30mL/min
calculated using the Cockcroft-Gault equation or a serum creatinine less than 2.0.
- Patient should have adequate hepatic function, defined as aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) ≤ 3x the upper limit of normal (ULN) and
serum direct bilirubin ≤ 2.0 x ULN. Patient with leukemic organ involvement as
assessed by the study investigator, must have a serum direct bilirubin ≤ 5.0 x ULN.
- Patient who has previously had an autologous or allogeneic stem cell transplant for
AML is allowed on study.
- Female patient of childbearing potential must have had a negative pregnancy test
within 7 days of initiation of dosing and must agree to use two acceptable methods
of birth control while on treatment. A woman must agree to remain on a highly
effective method throughout the study and for at least 6 months after the last dose
of study drug. A female is considered fertile following menarche and until becoming
postmenopausal unless permanently sterile.
- Male participants with female partners of childbearing potential are eligible for
participation in the study if they agree to the following during treatment and until
the end of relevant systemic exposure defined as 6 months after final drug
administration.
Exclusion Criteria:
- Patient has a diagnosis of acute promyelocytic leukemia (APL).
- Patient on any other investigational anti-cancer agents.
- Patient has active uncontrolled systemic fungal, bacterial, or viral infection.
- Patient has presence of any other condition that may increase the risk associated
with study participation, and in the opinion of the investigator, would make the
patient inappropriate for entry into the study.
- Patient has immediate life-threatening, severe complications of leukemia such as
uncontrolled bleeding, pneumonia with hypoxia or shock, and/or severe disseminated
intravascular coagulation.
- Patient has significant active cardiac disease within 6 months prior to the start of
study treatment, including New York Heart Association (NYHA) class III or IV
congestive heart failure; acute coronary syndrome (ACS); and/or ischemic stroke.
- Patient has left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO)
or multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of
study treatment.
- Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other
conditions that limit the ingestion or gastrointestinal absorption of drugs
administered orally.
- Patient has a medical history of progressive multifocal leukoencephalopathy.
- Patient has QTc interval (i.e., Fridericia's correction [QTcF]) ≥ 450 ms (mean of
triplicate ECG) or other factors that increase the risk of QT prolongation or
ventricular arrhythmic events (e.g. family history of long QT interval syndrome).
Patients with a QTcF over 450 ms due to a bundle branch block or a pacemaker may
participate in the study with approval of the study principal investigator.
- Patient has active graft-versus-host disease. However patients with isolated skin
GVH controlled with topical steroids are eligible to participate
- Female patient who is pregnant or lactating.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Basking Ridge
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eytan Stein, MD
Phone:
646-608-3749
Facility:
Name:
Memorial Sloan Kettering Monmouth
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eytan Stein, MD
Phone:
646-608-3749
Facility:
Name:
Memorial Sloan Kettering Bergen
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eytan Stein, MD
Phone:
646-608-3749
Facility:
Name:
Memorial Sloan Kettering Suffolk-Commack
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eytan Stein, MD
Phone:
646-608-3749
Facility:
Name:
Memorial Sloan Kettering Westchester
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eytan Stein, MD
Phone:
646-608-3749
Contact backup:
Last name:
Eytan Stein, MD
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eytan Stein, MD
Phone:
646-608-3749
Contact backup:
Last name:
Aaron Goldberg, MD, Phd
Phone:
646-608-3752
Facility:
Name:
Memorial Sloan Kettering Nassau
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Eytan Stein, MD
Phone:
646-608-3749
Start date:
June 26, 2023
Completion date:
February 2025
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Astellas Pharma US, Inc.
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05756777
http://www.mskcc.org/mskcc/html/44.cfm
