RECRUITING

Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 Syndrome (hrMDS). Patients enrolling in the Phase 1 dose escalation of the study must meet one of the following criteria prior to consenting to the study: * Relapse/refractory (R/R) AML with FMS-like tyrosine kinase-3 (FLT3) mutations who have been previously treated with a FLT3 inhibitor * R/R AML with spliceosome mutations of splicing factor 3B subunit 1 (SF3B1) or U2AF1 * R/R hrMDS with spliceosome mutations of SF3B1 or U2 small nuclear RNA auxiliary factor 1 (U2AF1) * Number of pretreatments: 1 or 2 The Phase 2a Dose Expansion will be in 3 Cohorts of patients: 1. R/R AML with FLT3 mutations who have been previously treated with a FLT3 inhibitor; 2. R/R AML with spliceosome mutations of SF3B1 or U2AF1; and 3. R/R hrMDS (Revised International Prognostic Scoring System \[IPSS-R\] score \> 3.5) with spliceosome mutations of SF3B1 or U2AF1. All patients above have had ≤ 2 lines of prior systemic anticancer treatment. In previous versions of this protocol there was a Phase 1b portion of the study, in which patients with AML or hrMDS received CA-4948 in combination with venetoclax. This part of the study is no longer open for enrollment.

Official Title

A Phase 1/2A, Open Label Dose Escalation and Expansion Study of Orally Administered CA-4948 as a Monotherapy in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Quick Facts

Study Start:2020-07-06
Study Completion:2026-04-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04278768

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Males and females ≥18 years of age
  2. 2. Life expectancy of at least 3 months
  3. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1
  4. 4. Cytomorphology based confirmed diagnosis of MDS or AML (as per World Health Organisation \[WHO\] 2016 classification) with the following characteristics.
  5. * R/R AMLwith FLT3 mutations who have been previously treated with a FLT3 inhibitor
  6. * R/R AML with spliceosome mutations of SF3B1 or U2AF1
  7. * R/R hrMDS (IPSS-R score \> 3.5) with spliceosome mutations of SF3B1 or U2AF1
  8. * Number of pretreatments: 1 or 2
  9. 5. Acceptable organ function at screening
  10. 6. Ability to swallow and retain oral medications
  11. 7. Negative serum pregnancy test in women of childbearing potential
  12. 8. 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 90 days after the last dose of emavusertib
  13. 9. Willing and able to provide written informed consent and comply with the requirements of the trial
  14. 10. Able to undergo serial bone marrow sampling and peripheral blood sampling
  1. 1. Diagnosed with acute promyelocytic leukemia (APL, M3)
  2. 2. Has known active central nervous system (CNS) leukemia
  3. 3. 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
  4. 4. Chronic myeloid leukemia (CML)
  5. 5. 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.
  6. 6. Use of any investigational agent within 3 weeks or 5 half-lives, whichever is shorter, prior to start of emavusertib
  7. 7. Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy, with the exception of alopecia that has not resolved to Grade ≤ 1within 7 days prior to start of emavusertib; presence of any acute or chronic non-hematological toxicity ≥ Grade 3 at Screening, or prior to start of emavusertib must resolve to ≤ Grade 2.
  8. 8. Known allergy or hypersensitivity to any component of the formulation of emavusertib
  9. 9. Major surgery, other than diagnostic surgery, \<28 days from the start of emavusertib; minor surgery \<14 days from the start of emavusertib
  10. 10. Patients with active advanced malignant solid tumors
  11. 11. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
  12. 12. 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
  13. 13. 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 \< 40% 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)
  14. 14. Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of emavusertib
  15. 15. Pregnant or lactating
  16. 16. Systemic fungal, bacterial, viral, or other infection that is not controlled
  17. 17. 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

Contacts and Locations

Study Contact

Catherine Wang, MD
CONTACT
617-503-6500
clinicaltrials@curis.com

Study Locations (Sites)

Moffitt Cancer Center
Tampa, Florida, 33612
United States
Winship Cancer Institute
Atlanta, Georgia, 30322
United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611
United States
University of Chicago Medical Center
Chicago, Illinois, 60637
United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130
United States
Albert Einstein Medical College
Bronx, New York, 10461
United States
University of Rochester Medical Center
Rochester, New York, 14642
United States
Novant Health Hematology - Forsyth
Winston-Salem, North Carolina, 27103
United States
The Ohio State University Wexner Medical Center - James Cancer Hospital
Columbus, Ohio, 43210
United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
United States

Collaborators and Investigators

Sponsor: Curis, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-07-06
Study Completion Date2026-04-01

Study Record Updates

Study Start Date2020-07-06
Study Completion Date2026-04-01

Terms related to this study

Keywords Provided by Researchers

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • AML
  • MDS
  • Interleukin-1 receptor-associated kinase 4 (IRAK4)
  • FLT3-ITD or TKD mutant
  • FLT3 Wild Type (WT)
  • Relapse/refractory to hypermethylating agent (HMA)
  • spliceosome mutation
  • SF3B1
  • U2AF1
  • Serine/arginine-rich splicing factor 2 (SRSF2)
  • Zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2 (ZRSR2)
  • higher-risk MDS
  • failing prior treatment
  • R/R AML or relapse/refractory AML
  • R/R hrMDS or relapse/refractory hrMDS
  • FLT3 mutation
  • FLT3 inhibitor

Additional Relevant MeSH Terms

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome