Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
The researchers are doing this study to find out whether E7820 is an effective treatment for
people with relapsed/refractory myeloid cancers with mutations in splicing factor genes.
Participants will have acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or
chronic myelomonocytic leukemia (CMML).
Phase
Phase 2
Funding Agency/Sponsor
Institutional
Disease
Leukemia
Enrollment Eligibility
Inclusion Criteria:
1. Subject is ≥ 18 years of age at the time of signing informed consent 2. Subject is
willing and able to adhere to the study visit schedule and other protocol requirements. 3.
Subject has relapsed or refractory MDS, AML or CMML with a previously defined hotspot
splicing factor mutation in SF3B1, SRSF2, U2AF1, or U2AF2 (with hotspot mutations as
defined by OncoKB) or a nonsense or frameshift mutation in ZRSR2. A splicing factor
mutation is required to be detected on next generation sequencing from bone marrow aspirate
or peripheral blood at any timepoint within the 6 months prior to screening for the study.
a. Relapsed AML is defined as: i. The appearance of 5% or greater myeloblasts in the bone
marrow or peripheral blood after achieving a CR (MRD positive or negative), CRh, or CRi
1. Patients with mutations in FLT3, IDH1 or IDH2 must have failed or been intolerant of an
FDA approved FLT3, IDH1 or IDH2 inhibitor before enrolling on study.
b. Refractory AML is defined as failure to achieve a CR, CRh, or CRi after one of the
following regimens: i. Two cycles of intensive induction chemotherapy with a cytarabine
containing regimen (e.g. 7+3, MEC, HIDAC, etc.) ii. Two cycles of HMA/venetoclax or
LDAC/glasdegib iii. 4 cycles of HMA monotherapy c. Relapsed MDS is defined as: i. Any
relapse after achieving an IWG defined response. d. Refractory MDS is defined as: i. For
patients with intermediate, high or very high risk disease by IPSS-R, the failure to
achieve a response (as per IWG 2006 criteria) after 4 cycles of HMA monotherapy or 2 cycles
of HMA + venetoclax.
ii. For patients with very low and low risk disease by IPSS-R failure to achieve
hematologic improvement or loss of hematologic improvement after treatment with standard of
care agents such as ESAs, Luspatercept (for MDS with ringed sideroblasts) and lenalidomide
(for pts with a 5q-).
e. Relapsed CMML is defined as: i. Any relapse after achieving an IWG defined response. f.
Refractory CMML is defined as: i. Failure to achieve a response (as per IWG 2006 criteria)
after 4 cycles of HMA monotherapy or 2 cycles of HMA + venetoclax.
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 5.
Subject has adequate organ function defined as:
1. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT)
and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to organ
involvement by the patient's myeloid malignancy (in that case a cut off of ≤ 5 x ULN
will be used)
2. Serum direct bilirubin < 1.5 x ULN.
3. Creatinine clearance ≥ 60 mL/min based on the Cockroft-Gault glomerular filtration
rate (GFR) estimation.
4. Females of childbearing potential may participate provided they have a negative serum
pregnancy test at screening and a negative serum OR urine pregnancy test within 72
hours of starting on treatment. Females and male participants with female partners of
childbearing potential also must agree to either abstain from sexual intercourse or
use a highly effective method of contraception while on study and for 4 months after
completing the study treatment.
6. There are no limits on transfusion and/or growth factor support for enrollment.
7. In case of leukemic organ involvement, patients with creatinine clearance > 30
ml/min and bilirubin ≤ 2.0 x ULN will be eligible to be included.
Exclusion Criteria:
1. Patients with acute promyelocytic leukemia
2. Subject has immediate life-threatening, severe complications of their myeloid
malignancy such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or
disseminated intravascular coagulation
3. Subject 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 stroke or 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.
4. Subject has active viral infection with human immunodeficiency virus (HIV), or
active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
Patients with HIV that is controlled with HAART are eligible to participate.
5. Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other
conditions that limit the ingestion or gastrointestinal absorption of drugs
administered orally.
6. Subject has active uncontrolled systemic fungal, bacterial, or viral infection
(defined as ongoing signs/symptoms related to the infection without improvement
despite appropriate antibiotics, antiviral therapy, and/or other treatment).
7. Subject has QTc interval (i.e., Fridericia's correction [QTcF]) ≥ 480 ms or other
factors that increase the risk of QT prolongation or arrhythmic events (e.g.,
heart failure family history of long QT interval syndrome) at screening. Patients
with left bundle branch block or right bundle branch block with prolonged QTc
will be allowed to enroll on the trial with medical monitor approval.
8. Female subject who is pregnant or lactating.
9. Subject with known hypersensitivity to sulfa medications