Status:
RECRUITING
Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)
Lead Sponsor:
Curis, Inc.
Conditions:
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This is a multicenter, open-label, Phase 1/2a dose escalation and expansion study of orally administered emavusertib (CA-4948) monotherapy in adult patients with AML or higher- risk Myelodysplastic Sy...
Detailed Description
The primary objective of the Phase 1 portion of the study is to determine the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D) for emavusertib in monotherapy in patients with AML, inte...
Eligibility Criteria
Inclusion
- Males and females ≥18 years of age
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1
- Cytomorphology based confirmed diagnosis of MDS or AML (as per World Health Organisation \[WHO\] 2016 classification) with the following characteristics.
- Phase 1 Dose Escalation (Monotherapy)
- • AML (primary or secondary, including treatment-related) after failing at least 1 standard treatment (may include chemotherapy, re induction therapy or stem cell transplantation).
- OR
- • Higher-risk R/R MDS that are considered resistant/refractory following at least 2 to 3 cycles of hypomethylating agent (HMA) or evidence of early progression
- Phase 2a Dose Expansion (Monotherapy)
- Patients with:
- R/R AMLwith FLT3 mutations who have been previously treated with a FLT3 inhibitor
- R/R AML with spliceosome mutations of SF3B1 or U2AF1
- R/R hrMDS (IPSS-R score \> 3.5) with spliceosome mutations of SF3B1 or U2AF1
- Number of prior treatments: 1 or 2
- Acceptable organ function at screening
- Ability to swallow and retain oral medications
- Negative serum pregnancy test in women of childbearing potential
- Women of childbearing potential and men who partner with a woman of childbearing potential must agree to use highly effective contraceptive methods for the duration of the study and for 180 days after the last dose of emavusertib
- Willing and able to provide written informed consent and comply with the requirements of the trial
- Able to undergo serial bone marrow sampling and peripheral blood sampling
Exclusion
- Diagnosed with acute promyelocytic leukemia (APL, M3)
- Has known active central nervous system (CNS) leukemia
- Allogeneic hematopoietic stem cell transplant (Allo-HSCT) within 60 days of the first dose of emavusertib, or clinically significant graft-versus-host disease (GVHD) requiring ongoing up titration of immunosuppressive medications prior to start of emavusertib
- Chronic myeloid leukemia (CML)
- Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 3 weeks (or 5 half-lives) prior to start of emavusertib.
- Localized radiation or surgical resection of skin cancers allowed.
- Use of any investigational agent within 3 weeks or 5 half-lives, whichever is shorter, prior to start of emavusertib
- Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy, with the exception of alopecia that has not resolved to Grade ≤ 1 within 7 days prior to start of emavusertib.
- Known allergy or hypersensitivity to any component of the formulation of emavusertib
- Major surgery, other than diagnostic surgery, \<28 days from the start of emavusertib; minor surgery \<14 days from the start of emavusertib
- Patients with active advanced malignant solid tumors
- Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
- Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive or Hepatitis C virus (HCV) infection \<6 months prior to start of emavusertib unless viral load is undetectable, or HCV with cirrhosis
- Uncontrolled or severe cardiovascular disease including myocardial infarction or unstable angina within 6 months prior to CA-4948, New York Heart Association Class II or greater congestive heart failure, or left ventricular ejection fraction \< 50% by echocardiogram or multi-gated acquisition scan, serious arrhythmias uncontrolled on treatment, clinically significant pericardial disease, cardiac amyloidosis, congenital long QT syndrome, or QTc with Fridericia's correction (QTcF) that is unmeasurable or \> 450 milliseconds (msec) on Screening electrocardiogram (ECG)
- Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of emavusertib
- Pregnant or lactating
- Systemic fungal, bacterial, viral, or other infection that is not controlled
- Any other severe, acute, or chronic medical, psychiatric or social condition, or laboratory abnormality that may increase the risk of trial participation or emavusertib administration
Key Trial Info
Start Date :
July 6 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
April 1 2026
Estimated Enrollment :
366 Patients enrolled
Trial Details
Trial ID
NCT04278768
Start Date
July 6 2020
End Date
April 1 2026
Last Update
August 17 2025
Active Locations (32)
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1
Moffitt Cancer Center
Tampa, Florida, United States, 33612
2
Winship Cancer Institute
Atlanta, Georgia, United States, 30322
3
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
4
University of Chicago Medical Center
Chicago, Illinois, United States, 60637