Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With Acute Myelogenous Leu… (NCT04278768) | Clinical Trial Compass
SuspendedPhase 1/2
Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)
Stopped: Dosing completed in all cohorts. Planning underway for potential additional patient cohorts.
United States, Czechia, France366 participantsStarted 2020-07-06
Plain-language 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 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.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. 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.
. Acceptable organ function at screening
. Ability to swallow and retain oral medications
. Negative serum pregnancy test in women of childbearing potential
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Determine Maximum Tolerated Dose (MTD) of emavusertib (CA-4948) monotherapy (Phase 1)
Timeframe: 28 days
2
Determine the Recommended Phase 2 Dose (RP2D) of emavusertib monotherapy (Phase 1)
Timeframe: 24 months
3
Determine Maximum Tolerated Dose (MTD) of emavusertib in combination with venetoclax (Phase 1b)
Timeframe: 28 days
4
Determine the Recommended Phase 2 Dose (RP2D) of emavusertib in combination with venetoclax (Phase 1b)
Timeframe: 24 months
5
To assess anti-cancer activity (Phase 2a - AML patients)
Timeframe: 24 months
6
To assess anti-cancer activity (Phase 2a - hrMDS patients)
. 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
Exclusion criteria
. 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.
. 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