NCT00102687

Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes

Completed Phase 2 Results posted Last updated 22 November 2019

What this trial tests

Phase 2 trial testing azacitidine in Myelodysplastic Syndromes in 151 participants. Completed in 1 August 2008.

Timeline

1 January 2005

Primary endpoint
1 August 2008

1 August 2008

Quick facts

Lead sponsor	Celgene
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	151
Start date	1 January 2005
Primary completion	1 August 2008
Estimated completion	1 August 2008
Sites	31 locations across United States

Drugs / interventions tested

• azacitidine (azacitidine) — full drug profile →

Conditions studied

• Myelodysplastic Syndromes — all drugs for Myelodysplastic Syndromes →

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Myelodysplastic Syndromes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period. Primary · Day 1 (randomization) to 6 months

Participant counts by best hematological response; complete remission(CR) is better than a partial remission(PR) which is better than stable disease(SD). Investigator determined responses followed IWG 2000 criteria for MDS CR: repeat bone marrow show \<5% myeloblasts, and peripheral blood evaluations lasting \>=2 months of hemoglobin(\>110 g/L), neutrophils(\>=1.5x10\^9/L), platelets(\>=100x10\^9/L), blasts (0%) and no dysplasia PR is the same as CR for peripheral blood: bone marrow shows blasts decrease by \>=50% or a less advanced FAB classification from pretreatment (see Population Descrip

Overall Response (CR+PR)

Group	Value	95% CI
Aza-5	4
Aza-5-2-2	3
Aza-5-2-5	4

Complete remission (CR)

Group	Value	95% CI
Aza-5	2
Aza-5-2-2	2
Aza-5-2-5	2

Partial remission (PR)

Group	Value	95% CI
Aza-5	2
Aza-5-2-2	1
Aza-5-2-5	2

Stable disease

Group	Value	95% CI
Aza-5	22
Aza-5-2-2	19
Aza-5-2-5	20

Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period. Primary · Day 1 (randomization) to 6 months

IWG 2000 Criteria: Pretreatment=hemoglobin \<110g/L or RBC transfusion-dependence, platelet count \<100x10\^9/L or platelet transfusion dependence, absolute neutrophil count \<1.5x10\^9/L. Erythroid response: Major-\>20g/L increase in hemoglobin or transfusion independence. Minor- 10-20g/L increase in hemoglobin or \>=50% decrease in transfusion requirements. Platelet response: Major-absolute increase of platelet count by \>=30x10\^9/L or platelet transfusion independence. Minor-\>=50% increase in platelet count with net increase \>10x10\^9/L but \<30x10\^9/L. (continued in Population Descr

Any Improvement n=50,49,47

Group	Value	95% CI
Aza-5	29
Aza-5-2-2	20
Aza-5-2-5	26

Erythroid response - Major n=44,43,41

Group	Value	95% CI
Aza-5	18
Aza-5-2-2	15
Aza-5-2-5	18

Erythroid response - Minor n=44,43,41

Group	Value	95% CI
Aza-5	4
Aza-5-2-2	1
Aza-5-2-5	2

Platelet response - Major n=24,28,28

Group	Value	95% CI
Aza-5	10
Aza-5-2-2	11
Aza-5-2-5	10

Platelet response - Minor n=24,28,28

Group	Value	95% CI
Aza-5	2
Aza-5-2-2	0
Aza-5-2-5	0

Neutrophil response - Major n=24,22,16

Group	Value	95% CI
Aza-5	4
Aza-5-2-2	3
Aza-5-2-5	3

Neutrophil response - Minor n=24,22,16

Group	Value	95% CI
Aza-5	2
Aza-5-2-2	0
Aza-5-2-5	0

Number of Participants With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period Primary · Day 1 (randomization) to 6 months

Number of participants whose best hematological outcome was either complete remission (CR), partial remission (PR) (as determined by the investigator), or any hematologic improvement (based on the IWG 2000 criteria for MDS). See previous outcomes for detailed definitions.

Group	Value	95% CI
Aza-5	30
Aza-5-2-2	20
Aza-5-2-5	27

Baseline Hemoglobin Values Secondary · Day 1 (randomization)

The median values for hemoglobin based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for hemoglobin. Baseline values are used to compare to values following treatment.

Group	Value	95% CI
Aza-5	94.0	63.0 – 131.0
Aza-5-2-2	98.0	70.0 – 135.0
Aza-5-2-5	95.5	59.0 – 145.0

Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months) Secondary · 6 months

The difference between hemoglobin values at the end of the initial study period minus the hemoglobin values at baseline.

Group	Value	95% CI
Aza-5	2.3	-25.9 – 41.8
Aza-5-2-2	2.9	-33.0 – 31.7
Aza-5-2-5	5.3	-20.4 – 30.4

Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period Primary · 24 months

Hematologic response during the maintenance period are compared to the response in the initial study period. Initial response could have been a complete remission, a partial remission, stable disease or a hematologic improvement. Maintenance period best response is after randomization to a maintenance arm for those randomized, and is after the start of cycle 7 for those remaining on initial period treatment throughout the study.

Improved response from initial study period

Group	Value	95% CI
Maintenance Aza 5 Days q 4 Weeks	7
Maintenance Aza 5 Days q 6 Weeks	10
Initial Period Treatment Continued Into Maintenance	12

Maintained response from initial study period

Group	Value	95% CI
Maintenance Aza 5 Days q 4 Weeks	6
Maintenance Aza 5 Days q 6 Weeks	5
Initial Period Treatment Continued Into Maintenance	10

Change From Baseline in Hemoglobin at the End of the Maintenance Study Period Secondary · 24 months

The difference between hemoglobin values at the end of the maintenance study period minus the hemoglobin values at baseline.

Group	Value	95% CI
Maintenance Aza 5 Days q 4 Weeks	5.9	-27.9 – 54.8
Maintenance Aza 5 Days q 6 Weeks	7.3	-14.4 – 55.5
Initial Period Treatment Continued Into Maintenance	14.5	-5.5 – 60.4

Baseline Platelet Values Secondary · Day 1 (randomization)

The median values for platelets based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for platelets. Baseline values are used to compare to values following treatment.

Group	Value	95% CI
Aza-5	110.0	9.0 – 516.0
Aza-5-2-2	90.0	8.0 – 581.0
Aza-5-2-5	86.0	8.0 – 699.0

Change From Baseline in Platelets at the End of Initial Study Period (6 Months) Secondary · 6 months

The difference between platelet values at the end of the initial study period minus the platelet values at baseline.

Group	Value	95% CI
Aza-5	4.8	-116.3 – 179.1
Aza-5-2-2	5.7	-145.6 – 192.6
Aza-5-2-5	12.6	-300.9 – 213.6

Change From Baseline in Platelets at the End of the Maintenance Study Period (Month 24) Secondary · 24 months

The difference between platelet values at the end of the maintenance study period minus the platelet values at baseline.

Group	Value	95% CI
Maintenance Aza 5 Days q 4 Weeks	19.8	-157.5 – 129.6
Maintenance Aza 5 Days q 6 Weeks	7.7	-279.8 – 166.3
Initial Period Treatment Continued Into Maintenance	17.3	-124.7 – 223.3

Baseline Absolute Neutrophil Count (ANC) Values Secondary · Day 1 (randomization)

The median values for ANC based on blood tests performed on study day 1 (prior to study treatment) constitute a baseline measure for ANC. Baseline values are used to compare to values following treatment.

Group	Value	95% CI
Aza-5	1.6	0.1 – 13.9
Aza-5-2-2	1.9	0.1 – 162.3
Aza-5-2-5	2.3	0.3 – 139.3

Change From Baseline in Absolute Neutrophil Count (ANC) at the End of Initial Study Period (6 Months) Secondary · 6 months

The difference between ANC values at the end of the initial study period minus the ANC values at baseline.

Group	Value	95% CI
Aza-5	-0.3	-4.6 – 1.9
Aza-5-2-2	-0.3	-35.9 – 1.4
Aza-5-2-5	-0.4	-9.7 – 8.5

Adverse events — posted to ClinicalTrials.gov

Time frame: The 3 groups in the Initial Period cover Day 1-6 months, and up to 24 months for participants that continued that treatment. The 2 Maintenance Period groups cover months 7-24 for subjects who were randomized to 1 of the 2 Maintenance treatment arms.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Aza-5

Serious: 18/50 (36%)

Deaths: —

Aza-5-2-2

Serious: 27/50 (54%)

Deaths: —

Aza-5-2-5

Serious: 22/48 (46%)

Deaths: —

Maintenance Aza 5 Days q 4 Weeks

Serious: 7/22 (32%)

Deaths: —

Maintenance Aza 5 Days q 6 Weeks

Serious: 13/21 (62%)

Deaths: —

Serious adverse events (103 terms)

Reaction	System	Aza-5	Aza-5-2-2	Aza-5-2-5	Maintenance Aza 5 Days q 4…	Maintenance Aza 5 Days q 6…
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Lobar pneumonia	Infections and infestations	—	—	—	—	—
Pancytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—
Bradycardia	Cardiac disorders	—	—	—	—	—
Cardiac valve vegetation	Cardiac disorders	—	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—	—
Myocardial ischaemia	Cardiac disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Colitis ischaemic	Gastrointestinal disorders	—	—	—	—	—
Colonic polyp	Gastrointestinal disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—
Enteritis	Gastrointestinal disorders	—	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—	—

Other adverse events (99 terms — click to expand)

Reaction	System	Aza-5	Aza-5-2-2	Aza-5-2-5	Maintenance Aza 5 Days q 4…	Maintenance Aza 5 Days q 6…
Nausea	Gastrointestinal disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Injection site erythema	General disorders	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Injection site pain	General disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Injection site pruritus	General disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Injection site bruising	General disorders	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Injection site desquamation	General disorders	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Pruritus generalised	Skin and subcutaneous tissue disorders	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—
Injection site rash	General disorders	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—

Most-reported serious reactions: Anaemia, Pneumonia, Febrile neutropenia, Urinary tract infection, Acute myeloid leukaemia, Myelodysplastic syndrome, Neutropenia, Thrombocytopenia.

Data from ClinicalTrials.gov NCT00102687 adverse events section.

Sponsor's own description

The purpose of this study is to determine if azacitidine, combined with Best Supportive Care (BSC), is effective in treating myelodysplastic syndromes (MDS) when given according to a different doses and dosing schedules.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Trials with 'epigenetic' drugs: an update.
   Nebbioso A, Carafa V, Benedetti R, Altucci L. · · 2012 · cited 162× · PMID 23103179 · DOI 10.1016/j.molonc.2012.09.004
2. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
   Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6
3. Epimutational profile of hematologic malignancies as attractive target for new epigenetic therapies.
   Fratta E, Montico B, Rizzo A, Colizzi F, et al · · 2016 · cited 17× · PMID 27329599 · DOI 10.18632/oncotarget.10033
4. Historical expectations with DNA methyltransferase inhibitor monotherapy in MDS: when is combination therapy truly "promising"?
   Brunner AM, Fell G, Steensma DP. · · 2022 · cited 3× · PMID 35143613 · DOI 10.1182/bloodadvances.2021006357