Treatment of anemia with CA-4948 in very low, low, or intermediate risk MDS patients.
- Conditions
- Anemia in patients with very low, low or intermediate risk myelodysplastic syndromes (MDS)MedDRA version: 21.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-003986-20-DE
- Lead Sponsor
- eipzig University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 84
- MDS OR MDS/MPN including MDS/MPN-RS-T, MDS/MPNu, aCML or CMML
- IPSS-R up to 3.5: very low/low/intermediate risk disease (MDS); MDS/MPN < 10% bone marrow blasts; CPSS-Score low/intermediate for CMML
- Symptomatic anemia
- Defined transfusion strategy
- No available option of an approved MDS therapy and classification of prior erythropoiesis-stimulating agent (ESA) treatment as follows:
+ Cohort A: ESA exposed (and refractory or intolerant);
+ Cohort B: ESA naive AND serum erythropoietin level >200 U/L
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
Compliance with major study procedures
1. Inability to swallow and retain oral medications (> 10 pills)
2. Patient does not accept bone marrow sampling
3. Patient does not accept up to weekly peripheral blood sampling
Safety
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of =3
5. Inacceptable organ function:
a. Serum creatinine >2 × ULN or calculated creatinine clearance < 30 ml/min
b. Aspartate aminotransferase (AST) > 2 × ULN OR alanine aminotransferase (ALT) > 2 × ULN
c. Total bilirubin >2 × ULN
i. exception >3 × ULN in patients with documented Gilbert’s syndrome
Interfering treatments
6. Prior treatment with azacitidine (injectable or oral) or decitabine.
7. The patient medically requires treatment with the following drugs that are forbidden during the trial or was exposed to one of these 14 days before registration:
a) Erythropoiesis stimulating agent (ESA) or luspatercept,
b) Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)
c) Lenalidomide
d) Another investigational drug or device, or approved therapy for investigational use
8. Iron chelation therapy
9. Major surgery within 28 days prior to registration.
Concomitant diseases
10. Known human immunodeficiency virus (HIV) infection
11. Active infectious hepatitis (Type B (HBV) or Type C (HCV)
12. Hepatitis virus detectable within 6 months before registration in patients with a history of hepatitis
13. History of other invasive malignancy, unless definitively treated with curative intent, provided it is deemed to be at low risk for recurrence by the treating physician
14. Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy that has not resolved to Grade =1 (except anemia and alopecia), as determined by NCI CTCAE v 5.0
15. Known allergy or hypersensitivity to any component of the formulation of CA-4948 used in this study
16. Severe cardiovascular disease
Formal requirements
17. Positive serum pregnancy test in women of childbearing potential
18. Women of childbearing potential and men who partner with a woman of childbearing potential unwilling to use highly effective contraceptive methods for the duration of the study and for 90 days after the last dose of CA-4948
19. Age under 18 years at registration
20. Inability to provide written informed consent (Subject without legal capacity who is unable to understand the nature, scope, significance and consequences of this clinical trial)
21. Simultaneous participation in another interventional clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 28 days prior registration
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the proportion of patients who have an erythroid response (HI-E) according to IWG 2018 criteria separately for both independent substudies.;Secondary Objective: - HI-E response duration <br>- Time to HI-E<br>- Hemoglobin changes from baseline<br>- Red blood cell transfusion (RBC) independence = 8 and = 12 weeks<br>- Frequency of RBC transfusions in transfusion dependent patients<br>- Neutrophil and platelet (HI-N and HI-P) responses<br>- Disease progression according to IWG 2018 criteria<br>- Safety and toxcicity profile of CA-4948<br>- Quality of life (QoL) <br>- Mutational pattern and burden of selected genes and their influence on response<br>;Primary end point(s): The primary efficacy endpoint is erythroid response (HI-E) according to IWG 2018 criteria ;Timepoint(s) of evaluation of this end point: After 4 cycles CA-4948 treatment.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • HI-E response duration <br>• Time to HI-E <br>• Frequency of RBC transfusions in transfusion dependent patients<br>• Neutrophil and platelet (HI-N and HI-P) responses according to IWG 2018 criteria <br>;Timepoint(s) of evaluation of this end point: - HI-E response duration: from time point of response determination (after start of treatment) until loss of response<br>Time to HI-E: time from start of treatment until HI-E determination