MDSPhase 2FLO_CC-486-NCT04806906
Pilot Study of CC 486 (Oral Azacitidine) Plus BSC as Maintenance After sc Azacitidine in Elderly HR-IPSS-R MDS Patients
A Phase 2 study testing CC-486 in people with MDS and CMML, run by University of Florence at 1 site in Italy.
Trial summary
Treatment of higher-risk (intermediate, high and very high) Myelodysplastic Syndromes (MDS) according to the revised International Prognostic Scoring System (IPSS-R) who obtained a stable hematological response ( CR, PR) after subcutaneous azacitidine treatment. Read more about this study
- Who is it for?
- Ages 65 to 100 years
- What is being tested?
- CC-486
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteItaly
- Study dates
- 24 Mar 2021to 24 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 100 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- Male or female subjects ≥ 65 years of age at the time of signing the ICD;
- 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)
Show all 13Show fewer
- myelodysplastic CMML (included in IPSS scoring, WBC < 13.x 109/L);
- Should have undergone therapy with subcutaneous azacitidine for at least 4-6 cycles ( + 2 cycles)
- Must have achieved CR/CRi, PR or SD with HI status, as evidenced by IWG Criteria 2006 ( APPENDIX E):
- ECOG performance status of 0, 1, 2 (Appendix C);
- Adequate bone marrow function based on ANCs ≥ 1.0 x 109/L and platelet counts ≥ 70 x 109/L.
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Treatment of higher-risk (intermediate, high and very high) Myelodysplastic Syndromes (MDS) according to the revised International Prognostic Scoring System (IPSS-R) who obtained a stable hematological response ( CR, PR) after subcutaneous azacitidine treatment.
Azacitidine is administered in hospital in a day care regimen, in Italy only by subcutaneous injection. The long duration of therapy obliges patients to travel to the hospital regularly, with evident worsening quality of life, both for patients and caregivers, although balanced by prolongation of survival and hematological improvement. Many patients stop therapy or are reluctant to continue because of the dependence from caregivers and hospital care.
This clinical study will evaluate the efficacy and safety of oral azacitidine (CC-486) plus best supportive care in subjects with higher-risk (intermediate, high and very high) Myelodysplastic Syndrome (MDS) according to the revised International Prognostic Scoring System (IPSS-R) and (high and INT-2) according to IPSS who obtained a stable hematological response (CR, PR, SD with HI) after at least 4-6 cycles of subcutaneous azacitidine treatment and maintained for 2 additional cycles.
Read the detailed description
Azacitidine therapy is effective in prolonging survival in higher risk MDS patients provided therapy is administered at 28 day-cycles until progression or loss of response.
A study conducted several years ago shows that although most responses to azacitidine occurred within 6 cycles, continued azacitidine therapy led to a further improvement in response category in almost half (48%) of all responders with a median of 3 additional cycles, and that 92% of patients achieved their best response by Cycle 12. In a randomized phase 3 trial conducted by the US Cancer and Leukemia Group B, which compared azacitidine with best supportive care, most responses occurred during the third or fourth month of azacitidine therapy. The phase 3 Cancer and Leukemia Group B study also showed that 90% of responses occurred within the first 6 cycles of treatment and that best response generally occurred 2 cycles after the first response-all of which is consistent with the current findings. Taken together, these data suggest that although some effects of azacitidine manifest promptly, additional courses are usually necessary before best response is achieved. Therefore, continuing azacitidine therapy offers the best chance of enhanced benefit if treatment is tolerated and there is no evidence of disease progression.
Azacitidine may affect the differentiation and growth of the MDS clone without necessarily eradicating it, suggesting that repetitive and prolonged exposure to azacitidine may be necessary for both the initial effects and the subsequent augmentation of response. Discontinuation of azacitidine therapy is in fact invariably followed by loss of response, disease progression and short survival. Treatment should be optimized to deliver at least 6 cycles, and in responsive patients until progression. In clinical practice, however, AZA is often discontinued after few cycles. Prematurely interrupted therapy could be the cause of inferior outcomes registered in "real life" studies. This inconsistency may be due to differences in adherence to dose, schedule, and minimum number of cycles, as well as to the management of patients with severe comorbidities. Proper management of first-line azacitidine therapy, with appropriate doses and prolonged treatment, may partially reduce primary resistance. This is why it is extremely important to maintain treatment until progression, despite scarce compliance of the patients to subcutaneous injections. Anyhow, it is clear that the azacitidine effect is transient, with responses maintained for 6 to 24 months.
Survival of the patients with refractory/relapsed disease is extremely short. A premature arrest of treatment may thus provoke loss of response and accelerate progression. In order to improve the compliance to treatment of MDS patients who have shown optimal responses to azacitidine, an oral formulation of the drug could indeed be advantageous. Oral therapy with CC 486 could free patients from hospital and caregiver dependence, as well as from injection site reactions, consequently improving quality of life, without altering the necessary continuation of treatment. During the present Covid-19 outbreak it has became even clearer that treatment with medications in oral formulation, under strict control of treating physicians, may indeed, beyond improving quality of life, decrease the risk of exposure to infections derived by in hospital administered therapy for MDS patients.
An oral formulation of azacitidine like cc486 provides an opportunity to deliver the drug at lower systemic doses over a more prolonged schedule that can be practically achieved with parenteral therapy. In addition, an oral formulation that can be taken at home rather than in the hospital/clinic setting represents an opportunity for patients with MDS to have a more convenient route of administration, thus alleviating the morbidity of injection and avoiding the inconvenience and resource utilization costs associated with frequent hospital/clinic visits. In addition, intervention with azacitidine in patients with MDS that have obtained a response after sc azacitidine may offer better quality of life and possibly a survival advantage.
- Being tested
- CC-486
- Keywords
- Azacitidine, Therapy, DNA methylation analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-486Drug
Also called Oral Azacitidine
Investigational product will be dispensed on Day 1 of each treatment cycle. 300 mg CC-486 QD for 14 days of each 28-day treatment cycle
| Study group | Role | What they receive |
|---|---|---|
| CC-486 | Experimental | subjects will receive 300 mg CC-486 QD for 14 days of each 28-day treatment cycle Receives: Drug: CC-486 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maintenance or improvement of response to therapy after switching from sc azacitidine to (oral) CC-486
Bone marrow aspirate will be performed before and after treatment, to evaluate maintenance of response according to IWG criteria. Assessment of complete and partial response, stable disease or progression will be provided by evaluating hematopoietic cell morphology. Routine interval of marrow assessments will be 4 months for safety. Marrow samples during treatment will be collected on Day 1 (± 7 days) every 4 cycles and at the Treatment Discontinuation visit. After Cycle 36, bone marrow aspiration collection and evaluation will occur if clinically indicated at the discretion of the Investigator. Additional bone marrow samples should be collected as clinically indicated. A bone marrow biopsy must be collected if adequate aspirate is not obtainable. Whenever a bone marrow sample is collected, a peripheral blood smear is to be prepared. Bone marrow cytogenetic testing by complete karyotype analysis is to be completed whenever a bone marrow aspirate is performed.
Measured: 0-24 months
Safety and tolerability of cc 486
Safety assessments will consist of evaluating adverse events and concomitant medication/therapies used to treat them, secondary primary malignancy, hematology and serum chemistry parameters, body weight measurement, vital signs, physical examinations, clinical signs and symptoms, with great attention to GI symptoms, laboratory, pathological, radiological or surgical findings and pregnancy testing (for FCBP subjects). Urinalysis and ECG will be repeated whenever clinically indicated during treatment and according routine HR-MDS patient management. Second primary malignancies will be monitored as events of interest and should be included as part of the assessment of AEs throughout the duration of the study including post treatment follow-up period. Investigators are to report any second primary malignancy, regardless of causal relationship to CC-486, occurring at any time from signing of informed consent and until the last study visit.
Measured: 0-24 months
Patient reported outcome on health related quality of life during CC-486 treatment
The patients treated with CC-486 will receive the questionnaire EQ-5D (EQ-5D-3L), a standardized instrument measuring health outcome. It provides a simple descriptive profile and a single index value for health status. Original EQ-5D questionnaire has five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and three distinct levels of functioning within each aspect (no problems, some problems and extreme problems). Each item is rescaled so that a better response corresponds to a higher numerical value and better QoL. Transformation of raw scores into a 0-100 scale will be carried out to generate the standardized scores for each domain. The EQ-5D questionnaire should be completed prior to interaction with study personnel and prior to CC-486 administration on Day 1 of every Cycle. Exploratory QoL Questions (Physical Impairment Numeric Rating Scale) will also be utilized in this clinical trial (scale 0-100).
Measured: 0-24 months
Secondary outcomes (3)
Time to relapse from CR/CRi, PR or SD with HI
The number of months elapsed from beginning of CC486 treatment to loss of marrow response will be evaluated . The first assessment of bone marrow status for maintenance or loss of response (CR/CRi, PR and SD with HI) will occur at Cycle 4. If response is maintained or improved, subjects can continue on to Cycle 5 and beyond. Subjects will be further assessed for response status every 4 cycles and at the Treatment Discontinuation visit. Assessment of marrow response will be performed at the discretion of the investigator in case of alterations in blood counts or unexpected cytopenias.
Measured: 0-24 months
Time to discontinuation of treatment
The number of months elapsed from beginning of CC486 treatment and its end wil be evaluated.
Subjects will be discontinued from treatment when they meet the following criteria:
Loss of response and/or progression to AML as demonstrated by bone marrow aspiration and peripheral blood counts Completion of study treatment Unacceptable toxicity
Measured: 0-24 months
Overall survival
The number of months elapsed from beginning of CC486 treatment to death
Measured: 0-60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start24 Mar 2021
- Primary completion24 Jan 2025
- Study completion24 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (43)Papers the sponsor has linked to this study.
- Other trials for MDSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florence
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Valeria Santini, University of Florence
- Investigators
- Valeria Santini, MD, Study chair, University of Florence- AOU Careggi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04806906
- Sponsor's protocol ID
- University of Florence
- Acronym
- FLO_CC-486-
- Status last verified
- Apr 2026
- First submitted
- 23 Feb 2021
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11.
PubMed 27069254Agrawal K, Das V, Vyas P, Hajduch M. Nucleosidic DNA demethylating epigenetic drugs - A comprehensive review from discovery to clinic. Pharmacol Ther. 2018 Aug;188:45-79. doi: 10.1016/j.pharmthera.2018.02.006. Epub 2018 Feb 15.
PubMed 29454856Bejar R, Stevenson KE, Caughey B, Lindsley RC, Mar BG, Stojanov P, Getz G, Steensma DP, Ritz J, Soiffer R, Antin JH, Alyea E, Armand P, Ho V, Koreth J, Neuberg D, Cutler CS, Ebert BL. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. J Clin Oncol. 2014 Sep 1;32(25):2691-8. doi: 10.1200/JCO.2013.52.3381. Epub 2014 Aug 4.
PubMed 25092778Bernal T, Martinez-Camblor P, Sanchez-Garcia J, Sanz G. Effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes in daily practice: the authors' reply. Leukemia. 2016 Mar;30(3):740-1. doi: 10.1038/leu.2015.339. Epub 2016 Jan 12. No abstract available.
PubMed 26754826Benson AB 3rd, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA Jr, McCallum R, Mitchell EP, O'Dorisio TM, Vokes EE, Wadler S. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004 Jul 15;22(14):2918-26. doi: 10.1200/JCO.2004.04.132.
PubMed 15254061Cabrero M, Jabbour E, Ravandi F, Bohannan Z, Pierce S, Kantarjian HM, Garcia-Manero G. Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: retrospective analysis of survival after long-term follow-up. Leuk Res. 2015 May;39(5):520-4. doi: 10.1016/j.leukres.2015.03.006. Epub 2015 Mar 20.
PubMed 25828745Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.
PubMed 16609072Cogle CR, Scott BL, Boyd T, Garcia-Manero G. Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Oncologist. 2015 Dec;20(12):1404-12. doi: 10.1634/theoncologist.2015-0165. Epub 2015 Oct 13.
PubMed 26463870de Lima M, Oran B, Champlin RE, Papadopoulos EB, Giralt SA, Scott BL, William BM, Hetzer J, Laille E, Hubbell B, Skikne BS, Craddock C. CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes. Biol Blood Marrow Transplant. 2018 Oct;24(10):2017-2024. doi: 10.1016/j.bbmt.2018.06.016. Epub 2018 Jun 20.
PubMed 29933073Diesch J, Zwick A, Garz AK, Palau A, Buschbeck M, Gotze KS. A clinical-molecular update on azanucleoside-based therapy for the treatment of hematologic cancers. Clin Epigenetics. 2016 Jun 21;8:71. doi: 10.1186/s13148-016-0237-y. eCollection 2016.
PubMed 27330573Dinmohamed AG, van Norden Y, Visser O, Posthuma EF, Huijgens PC, Sonneveld P, van de Loosdrecht AA, Jongen-Lavrencic M. Effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes in daily practice: results from the Dutch population-based PHAROS MDS registry. Leukemia. 2015 Dec;29(12):2449-51. doi: 10.1038/leu.2015.220. Epub 2015 Sep 15. No abstract available.
PubMed 26369829Duong VH, Lin K, Reljic T, Kumar A, Al Ali NH, Lancet JE, List AF, Komrokji RS. Poor outcome of patients with myelodysplastic syndrome after azacitidine treatment failure. Clin Lymphoma Myeloma Leuk. 2013 Dec;13(6):711-5. doi: 10.1016/j.clml.2013.07.007. Epub 2013 Sep 17.
PubMed 24054159Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21.
PubMed 19230772Fenaux P, Bowen D, Gattermann N, Hellstrom-Lindberg E, Hofmann WK, Pfeilstocker M, Sanz G, Santini V. Practical use of azacitidine in higher-risk myelodysplastic syndromes: an expert panel opinion. Leuk Res. 2010 Nov;34(11):1410-6. doi: 10.1016/j.leukres.2010.05.021. Epub 2010 Jul 6.
PubMed 20609474Figueroa ME, Skrabanek L, Li Y, Jiemjit A, Fandy TE, Paietta E, Fernandez H, Tallman MS, Greally JM, Carraway H, Licht JD, Gore SD, Melnick A. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood. 2009 Oct 15;114(16):3448-58. doi: 10.1182/blood-2009-01-200519. Epub 2009 Aug 3.
PubMed 19652201
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04806906
- Acronym / sponsor ID
- FLO_CC-486- / University of Florence
- Keywords
- Azacitidine, Therapy, DNA methylation analysis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of FlorenceUniversity, hospital or other
- Study start
- 24 Mar 2021 (actual)
- Primary completion
- 24 Jan 2025 (actual)
- Study completion
- 24 Jan 2025 (actual)
- First posted
- 19 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment of higher-risk (intermediate, high and very high) Myelodysplastic Syndromes (MDS) according to the revised International Prognostic Scoring System (IPSS-R) who obtained a stable hematological response ( CR, PR) after subcutaneous azacitidine treatment.
Azacitidine is administered in hospital in a day care regimen, in Italy only by subcutaneous injection. The long duration of therapy obliges patients to travel to the hospital regularly, with evident worsening quality of life, both for patients and caregivers, although balanced by prolongation of survival and hematological improvement. Many patients stop therapy or are reluctant to continue because of the dependence from caregivers and hospital care.
This clinical study will evaluate the efficacy and safety of oral azacitidine (CC-486) plus best supportive care in subjects with higher-risk (intermediate, high and very high) Myelodysplastic Syndrome (MDS) according to the revised International Prognostic Scoring System (IPSS-R) and (high and INT-2) according to IPSS who obtained a stable hematological response (CR, PR, SD with HI) after at least 4-6 cycles of subcutaneous azacitidine treatment and maintained for 2 additional cycles.
Detailed description
Azacitidine therapy is effective in prolonging survival in higher risk MDS patients provided therapy is administered at 28 day-cycles until progression or loss of response.
A study conducted several years ago shows that although most responses to azacitidine occurred within 6 cycles, continued azacitidine therapy led to a further improvement in response category in almost half (48%) of all responders with a median of 3 additional cycles, and that 92% of patients achieved their best response by Cycle 12. In a randomized phase 3 trial conducted by the US Cancer and Leukemia Group B, which compared azacitidine with best supportive care, most responses occurred during the third or fourth month of azacitidine therapy. The phase 3 Cancer and Leukemia Group B study also showed that 90% of responses occurred within the first 6 cycles of treatment and that best response generally occurred 2 cycles after the first response-all of which is consistent with the current findings. Taken together, these data suggest that although some effects of azacitidine manifest promptly, additional courses are usually necessary before best response is achieved. Therefore, continuing azacitidine therapy offers the best chance of enhanced benefit if treatment is tolerated and there is no evidence of disease progression.
Azacitidine may affect the differentiation and growth of the MDS clone without necessarily eradicating it, suggesting that repetitive and prolonged exposure to azacitidine may be necessary for both the initial effects and the subsequent augmentation of response. Discontinuation of azacitidine therapy is in fact invariably followed by loss of response, disease progression and short survival. Treatment should be optimized to deliver at least 6 cycles, and in responsive patients until progression. In clinical practice, however, AZA is often discontinued after few cycles. Prematurely interrupted therapy could be the cause of inferior outcomes registered in "real life" studies. This inconsistency may be due to differences in adherence to dose, schedule, and minimum number of cycles, as well as to the management of patients with severe comorbidities. Proper management of first-line azacitidine therapy, with appropriate doses and prolonged treatment, may partially reduce primary resistance. This is why it is extremely important to maintain treatment until progression, despite scarce compliance of the patients to subcutaneous injections. Anyhow, it is clear that the azacitidine effect is transient, with responses maintained for 6 to 24 months.
Survival of the patients with refractory/relapsed disease is extremely short. A premature arrest of treatment may thus provoke loss of response and accelerate progression. In order to improve the compliance to treatment of MDS patients who have shown optimal responses to azacitidine, an oral formulation of the drug could indeed be advantageous. Oral therapy with CC 486 could free patients from hospital and caregiver dependence, as well as from injection site reactions, consequently improving quality of life, without altering the necessary continuation of treatment. During the present Covid-19 outbreak it has became even clearer that treatment with medications in oral formulation, under strict control of treating physicians, may indeed, beyond improving quality of life, decrease the risk of exposure to infections derived by in hospital administered therapy for MDS patients.
An oral formulation of azacitidine like cc486 provides an opportunity to deliver the drug at lower systemic doses over a more prolonged schedule that can be practically achieved with parenteral therapy. In addition, an oral formulation that can be taken at home rather than in the hospital/clinic setting represents an opportunity for patients with MDS to have a more convenient route of administration, thus alleviating the morbidity of injection and avoiding the inconvenience and resource utilization costs associated with frequent hospital/clinic visits. In addition, intervention with azacitidine in patients with MDS that have obtained a response after sc azacitidine may offer better quality of life and possibly a survival advantage.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CC-486 | Experimental | Drug: CC-486subjects will receive 300 mg CC-486 QD for 14 days of each 28-day treatment cycle |
Who may qualify
- Ages
- 65 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (13 listed)
- Male or female subjects ≥ 65 years of age at the time of signing the ICD;
- Diagnosed, histologically confirmed at inclusion,
- Should have undergone therapy with subcutaneous azacitidine for at least 4-6 cycles ( + 2 cycles)
- Must have achieved CR/CRi, PR or SD with HI status, as evidenced by IWG Criteria 2006 ( APPENDIX E):
- ECOG performance status of 0, 1, 2 (Appendix C);
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CC-486Also: Oral AzacitidineInvestigational product will be dispensed on Day 1 of each treatment cycle. 300 mg CC-486 QD for 14 days of each 28-day treatment cycle | Drug | CC-486 |
Primary outcome
Maintenance or improvement of response to therapy after switching from sc azacitidine to (oral) CC-486
Time frame: 0-24 months
Bone marrow aspirate will be performed before and after treatment, to evaluate maintenance of response according to IWG criteria. Assessment of complete and partial response, stable disease or progression will be provided by evaluating hematopoietic cell morphology. Routine interval of marrow assessments will be 4 months for safety. Marrow samples during treatment will be collected on Day 1 (± 7 days) every 4 cycles and at the Treatment Discontinuation visit. After Cycle 36, bone marrow aspiration collection and evaluation will occur if clinically indicated at the discretion of the Investigator. Additional bone marrow samples should be collected as clinically indicated. A bone marrow biopsy must be collected if adequate aspirate is not obtainable. Whenever a bone marrow sample is collected, a peripheral blood smear is to be prepared. Bone marrow cytogenetic testing by complete karyotype analysis is to be completed whenever a bone marrow aspirate is performed.
Safety and tolerability of cc 486
Time frame: 0-24 months
Safety assessments will consist of evaluating adverse events and concomitant medication/therapies used to treat them, secondary primary malignancy, hematology and serum chemistry parameters, body weight measurement, vital signs, physical examinations, clinical signs and symptoms, with great attention to GI symptoms, laboratory, pathological, radiological or surgical findings and pregnancy testing (for FCBP subjects). Urinalysis and ECG will be repeated whenever clinically indicated during treatment and according routine HR-MDS patient management. Second primary malignancies will be monitored as events of interest and should be included as part of the assessment of AEs throughout the duration of the study including post treatment follow-up period. Investigators are to report any second primary malignancy, regardless of causal relationship to CC-486, occurring at any time from signing of informed consent and until the last study visit.
Patient reported outcome on health related quality of life during CC-486 treatment
Time frame: 0-24 months
The patients treated with CC-486 will receive the questionnaire EQ-5D (EQ-5D-3L), a standardized instrument measuring health outcome. It provides a simple descriptive profile and a single index value for health status. Original EQ-5D questionnaire has five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and three distinct levels of functioning within each aspect (no problems, some problems and extreme problems). Each item is rescaled so that a better response corresponds to a higher numerical value and better QoL. Transformation of raw scores into a 0-100 scale will be carried out to generate the standardized scores for each domain. The EQ-5D questionnaire should be completed prior to interaction with study personnel and prior to CC-486 administration on Day 1 of every Cycle. Exploratory QoL Questions (Physical Impairment Numeric Rating Scale) will also be utilized in this clinical trial (scale 0-100).
3 secondary outcomes
Time to relapse from CR/CRi, PR or SD with HI
Time frame: 0-24 months
Time to discontinuation of treatment
Time frame: 0-24 months
Overall survival
Time frame: 0-60 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Background: PubMed 27069254Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11.
- Background: PubMed 29454856Agrawal K, Das V, Vyas P, Hajduch M. Nucleosidic DNA demethylating epigenetic drugs - A comprehensive review from discovery to clinic. Pharmacol Ther. 2018 Aug;188:45-79. doi: 10.1016/j.pharmthera.2018.02.006. Epub 2018 Feb 15.
- Background: PubMed 25092778Bejar R, Stevenson KE, Caughey B, Lindsley RC, Mar BG, Stojanov P, Getz G, Steensma DP, Ritz J, Soiffer R, Antin JH, Alyea E, Armand P, Ho V, Koreth J, Neuberg D, Cutler CS, Ebert BL. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. J Clin Oncol. 2014 Sep 1;32(25):2691-8. doi: 10.1200/JCO.2013.52.3381. Epub 2014 Aug 4.
- Background: PubMed 26754826Bernal T, Martinez-Camblor P, Sanchez-Garcia J, Sanz G. Effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes in daily practice: the authors' reply. Leukemia. 2016 Mar;30(3):740-1. doi: 10.1038/leu.2015.339. Epub 2016 Jan 12. No abstract available.
- Background: PubMed 15254061Benson AB 3rd, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA Jr, McCallum R, Mitchell EP, O'Dorisio TM, Vokes EE, Wadler S. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004 Jul 15;22(14):2918-26. doi: 10.1200/JCO.2004.04.132.
- Background: PubMed 25828745Cabrero M, Jabbour E, Ravandi F, Bohannan Z, Pierce S, Kantarjian HM, Garcia-Manero G. Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: retrospective analysis of survival after long-term follow-up. Leuk Res. 2015 May;39(5):520-4. doi: 10.1016/j.leukres.2015.03.006. Epub 2015 Mar 20.
- Background: PubMed 16609072Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.
- Background: PubMed 26463870Cogle CR, Scott BL, Boyd T, Garcia-Manero G. Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Oncologist. 2015 Dec;20(12):1404-12. doi: 10.1634/theoncologist.2015-0165. Epub 2015 Oct 13.
- Background: PubMed 29933073de Lima M, Oran B, Champlin RE, Papadopoulos EB, Giralt SA, Scott BL, William BM, Hetzer J, Laille E, Hubbell B, Skikne BS, Craddock C. CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes. Biol Blood Marrow Transplant. 2018 Oct;24(10):2017-2024. doi: 10.1016/j.bbmt.2018.06.016. Epub 2018 Jun 20.
- Background: PubMed 27330573Diesch J, Zwick A, Garz AK, Palau A, Buschbeck M, Gotze KS. A clinical-molecular update on azanucleoside-based therapy for the treatment of hematologic cancers. Clin Epigenetics. 2016 Jun 21;8:71. doi: 10.1186/s13148-016-0237-y. eCollection 2016.
- Background: PubMed 26369829Dinmohamed AG, van Norden Y, Visser O, Posthuma EF, Huijgens PC, Sonneveld P, van de Loosdrecht AA, Jongen-Lavrencic M. Effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes in daily practice: results from the Dutch population-based PHAROS MDS registry. Leukemia. 2015 Dec;29(12):2449-51. doi: 10.1038/leu.2015.220. Epub 2015 Sep 15. No abstract available.
- Background: PubMed 24054159Duong VH, Lin K, Reljic T, Kumar A, Al Ali NH, Lancet JE, List AF, Komrokji RS. Poor outcome of patients with myelodysplastic syndrome after azacitidine treatment failure. Clin Lymphoma Myeloma Leuk. 2013 Dec;13(6):711-5. doi: 10.1016/j.clml.2013.07.007. Epub 2013 Sep 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Valeria Santini, MD study chair
University of Florence- AOU Careggi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CC-486 in people with MDS and CMML, run by University of Florence at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maintenance or improvement of response to therapy after switching from sc azacitidine to (oral) CC-486 (time frame: 0-24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04806906, which also lists 43 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.