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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01186939




Registration number
NCT01186939
Ethics application status
Date submitted
20/08/2010
Date registered
23/08/2010
Date last updated
14/11/2019

Titles & IDs
Public title
An Extension to Study AZA PH GL 2003 CL 001 Allowing for Continuation of Azacitidine Treatment in Patients With Myelodysplastic Syndromes (MDS)
Scientific title
AZA PH GL 2003 CL 001 - Extension A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)
Secondary ID [1] 0 0
AZA PH GL 2003 CL001 E
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine

Experimental: Azacitidine - Azacitidine (study drug) plus best supportive care.


Treatment: Drugs: Azacitidine
Azacitidine was injected subcutaneously (SC) for 7 days. The 7-day dosing was repeated every 28 days with dose adjustments allowed. The initial dose during the primary study was 75mg/m^2/day.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants in Different Categories of Treatment Emergent Adverse Events for the Extension Period
Timepoint [1] 0 0
43- 68 months

Eligibility
Key inclusion criteria
- Participants were considered eligible if they had been randomized to azacitidine
treatment in the primary study and were receiving azacitidine at the time of study
closure, had completed 12 months of treatment and observation in the primary study,
and had signed the informed consent document for the extension phase of the study.

- See study: AZA PH GL 2003 CL 001 for a list of inclusion criteria for the primary
study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- None specific to the extension phase of the study

- See study: AZA PH GL 2003 CL 001 for a list of exclusion criteria for the primary
study.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2009
Sample size
Target
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
- East Melbourne
Recruitment hospital [2] 0 0
- Herston
Recruitment hospital [3] 0 0
- Perth
Recruitment hospital [4] 0 0
- Woolloongabba
Recruitment postcode(s) [1] 0 0
- East Melbourne
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment postcode(s) [4] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Plovdiv
Country [2] 0 0
France
State/province [2] 0 0
Aulnay Sous Bois Cedex
Country [3] 0 0
Germany
State/province [3] 0 0
Berlin
Country [4] 0 0
Germany
State/province [4] 0 0
Dusseldorf
Country [5] 0 0
Germany
State/province [5] 0 0
Essen
Country [6] 0 0
Germany
State/province [6] 0 0
Kiel
Country [7] 0 0
Greece
State/province [7] 0 0
Crete
Country [8] 0 0
Greece
State/province [8] 0 0
Haidari
Country [9] 0 0
Hungary
State/province [9] 0 0
Budapest
Country [10] 0 0
Italy
State/province [10] 0 0
Bologna
Country [11] 0 0
Italy
State/province [11] 0 0
Firenze
Country [12] 0 0
Italy
State/province [12] 0 0
Genova
Country [13] 0 0
Italy
State/province [13] 0 0
Rome
Country [14] 0 0
Netherlands
State/province [14] 0 0
Nijmegen
Country [15] 0 0
Poland
State/province [15] 0 0
Lodz
Country [16] 0 0
Spain
State/province [16] 0 0
Avda Campanar
Country [17] 0 0
Spain
State/province [17] 0 0
Leon
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
At the conclusion of study AZA PH GL 2003 CL 001 (NCT00071799), eligible participants could
be enrolled in an optional extension phase in order to continue treatment with azacitidine
until it became commercially available; the continued treatment was for ethical and safety
reasons only and not to provide additional efficacy data.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01186939
Trial related presentations / publications
Fenaux 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.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. doi: 10.1200/JCO.2009.23.8329. Epub 2009 Dec 21.
Gore SD, Fenaux P, Santini V, Bennett JM, Silverman LR, Seymour JF, Hellstrom-Lindberg E, Swern AS, Beach CL, List AF. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial. Haematologica. 2013 Jul;98(7):1067-72. doi: 10.3324/haematol.2012.074831. Epub 2013 Apr 12.
Savona MR, Kolibaba K, Conkling P, Kingsley EC, Becerra C, Morris JC, Rifkin RM, Laille E, Kellerman A, Ukrainskyj SM, Dong Q, Skikne BS. Extended dosing with CC-486 (oral azacitidine) in patients with myeloid malignancies. Am J Hematol. 2018 Oct;93(10):1199-1206. doi: 10.1002/ajh.25216. Epub 2018 Sep 3.
Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellstrom-Lindberg E, Santini V, List AF, Gore SD, Backstrom J, McKenzie D, Beach CL. Effects of azacitidine compared with conventional care regimens in elderly (>/= 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol. 2010 Dec;76(3):218-27. doi: 10.1016/j.critrevonc.2010.04.005. Epub 2010 May 6.
Garcia-Manero G, Scott BL, Cogle CR, Boyd TE, Kambhampati S, Hetzer J, Dong Q, Kumar K, Ukrainskyj SM, Beach CL, Skikne BS. CC-486 (oral azacitidine) in patients with myelodysplastic syndromes with pretreatment thrombocytopenia. Leuk Res. 2018 Sep;72:79-85. doi: 10.1016/j.leukres.2018.08.001. Epub 2018 Aug 3.
Ma X, Steensma DP, Scott BL, Kiselev P, Sugrue MM, Swern AS. Selection of patients with myelodysplastic syndromes from a large electronic medical records database and a study of the use of disease-modifying therapy in the United States. BMJ Open. 2018 Jul 23;8(7):e019955. doi: 10.1136/bmjopen-2017-019955.
de 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.
Wehmeyer J, Zaiss M, Losem C, Schmitz S, Niemeier B, Harde J, Hannig CV, Harich HD, Muller J, Klausmann M, Tessen HW, Potthoff K. Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). Eur J Haematol. 2018 Dec;101(6):766-773. doi: 10.1111/ejh.13160. Epub 2018 Oct 25.
Platzbecker U, Middeke JM, Sockel K, Herbst R, Wolf D, Baldus CD, Oelschlagel U, Mutherig A, Fransecky L, Noppeney R, Bug G, Gotze KS, Kramer A, Bochtler T, Stelljes M, Groth C, Schubert A, Mende M, Stolzel F, Borkmann C, Kubasch AS, von Bonin M, Serve H, Hanel M, Duhrsen U, Schetelig J, Rollig C, Kramer M, Ehninger G, Bornhauser M, Thiede C. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018 Dec;19(12):1668-1679. doi: 10.1016/S1470-2045(18)30580-1. Epub 2018 Nov 12.
Boutault R, Peterlin P, Boubaya M, Sockel K, Chevallier P, Garnier A, Guillaume T, Le Bourgeois A, Debord C, Godon C, Le Bris Y, Theisen O, Kroschinsky F, Moreau P, Bene MC, Platzbecker U, Eveillard M. A novel complete blood count-based score to screen for myelodysplastic syndrome in cytopenic patients. Br J Haematol. 2018 Dec;183(5):736-746. doi: 10.1111/bjh.15626. Epub 2018 Nov 8.
Wenk C, Garz AK, Grath S, Huberle C, Witham D, Weickert M, Malinverni R, Niggemeyer J, Kyncl M, Hecker J, Pagel C, Mulholland CB, Muller-Thomas C, Leonhardt H, Bassermann F, Oostendorp RAJ, Metzeler KH, Buschbeck M, Gotze KS. Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis. Blood Adv. 2018 Dec 11;2(23):3447-3461. doi: 10.1182/bloodadvances.2018022053.
Zeidan AM, Klink AJ, McGuire M, Feinberg B. Treatment sequence of lenalidomide and hypomethylating agents and the impact on clinical outcomes for patients with myelodysplastic syndromes. Leuk Lymphoma. 2019 Aug;60(8):2050-2055. doi: 10.1080/10428194.2018.1551538. Epub 2019 Jan 14.
Leung KK, Nguyen A, Shi T, Tang L, Ni X, Escoubet L, MacBeth KJ, DiMartino J, Wells JA. Multiomics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell-surface proteome. Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):695-700. doi: 10.1073/pnas.1813666116. Epub 2018 Dec 24.
Craddock C, Slade D, De Santo C, Wheat R, Ferguson P, Hodgkinson A, Brock K, Cavenagh J, Ingram W, Dennis M, Malladi R, Siddique S, Mussai F, Yap C. Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia. J Clin Oncol. 2019 Mar 1;37(7):580-588. doi: 10.1200/JCO.18.00889. Epub 2019 Jan 17.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01186939