A Phase 2, Monocentric, Pilot Study to evaluate safety and efficacy of CC 486 (Oral Azacitidine) Plus Best Supportive Care as maintenance of response to sc azacitidine in IPSS higher risk elderly MDS patients

Phase 1

• Conditions: IPSS and IPSS-R higher Risk ( INT-2 and High risk IPSS; Intermediate, high and very high risk IPSS-R) elderly Myelodysplastic syndrome (MDS) patients; MedDRA version: 20.0Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-001165-36-IT
• Lead Sponsor: Dipartimento di Medicina Sperimentale e Clinica- Università di Firenze

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-02-10
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female subjects = 65 years of age at the time of signing the ICD;
2. Diagnosed, histologically confirmed at inclusion,
- Int-2 or High according to IPSS, or
- Very High, High or Intermediate according to IPSS-R, or
- Hypoplastic AML (20-30% BM blasts, previosuly considered MDS RAEB-T)
- myelodysplastic CMML (included in IPSS scoring, WBC < 13.x 109/L);
3. Should have undergone therapy with subcutaneous azacitidine for at least 4-6 cycles
( + 2 cycles)
4. Must have achieved CR/CRi, PR or SD with HI status, as evidenced by IWG Criteria 2006 ( APPENDIX E):
5. ECOG performance status of 0, 1, 2 (Appendix C);
6. Adequate bone marrow function based on ANCs = 1.0 x 109/L and platelet counts = 70 x 109/L.
7. Adequate organ function, defined as:
Serum bilirubin =1.5 times the upper limit of normal (ULN);
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 times the ULN;
Serum creatinine = 2.5 times the ULN;
8.Male subjects with a female partner of childbearing potential must agree to practice abstinence or to the use of a physician-approved contraceptive method throughout the course of the study and avoid fathering a child during the course of the study and for 3 months following the last dose of azacitidine;
10. Understand and voluntarily sign an ICD prior to any study related assessments/procedures are conducted;
11. Able to adhere to the study visit schedule and other protocol requirements;
12. Ability to swallow study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

- Absence of confirmed hematological response ( IWG HI/PR/CR) after at least 4 to 6 months of azacitidine sc and maintenance of response for 2 additional cycles.
- Inability to provide a valid informed consent.
- Eligibility for HSCT
- Active infection
- Serum creatinine > 2 x ULN at screening.
- ECOG performance status > 2
- Left ventricular ejection fraction < 50% by echocardiography
- A history of repeated hospitalization for severe infections Systemic diseases that would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.)
- Clinical or laboratory evidence of chronic Hepatitis B or Hepatitis C (definition of chronic hepatitis follows EASL 2017 criteria).
- History of HIV positive test result (ELISA or Western blot).
- ALT or AST over 3 times superior to ULN at screening.
- Total bilirubin over 1.5 times superior to ULN at screening (patients with Gilbert syndrome are allowed to enter the study)
- Patients participating in another clinical trial other than an observational registry study.
- Patients with a history of another malignancy within the past 3 years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ.
- History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative.
- Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug.
- History of drug or alcohol abuse within the 12 months prior to enrollment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified