Trial Outcomes & Findings for Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome (NCT NCT01165996)

Last Updated: 2019-03-04

Results Overview

Complete Response (CR) include less than 5% marrow blasts without evidence of dysplasia and normalization of peripheral blood counts, including a hemoglobin level of 110 g/L or more, a neutrophil count of 1.5 × 109/L or more, and a platelet count of 100 × 109/L or more. For PR, patients must demonstrate all CR criteria if abnormal before treatment except that marrow blasts should decrease by 50% or more compared with pretreatment levels, or patients may demonstrate a less-advanced MDS disease category than prior to treatment. Stable disease (SD) is defined by failure to achieve at least a partial response but no evidence of progression. Disease progression (DP) includes at least 50% decrease from maximum remission in granulocytes or platelets, reduction in hemoglobin by greater than or equal to 2g/dL, or transfusion dependence. Hematologic improvement (HI) includes hemoglobin increase by at least 1.5g/dL, reduction in transfusions, increase of platelets, increase of neutrophil count

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Formal assessment at week 12 for study primary end-point (hematologic improvement).

Results posted on

2019-03-04

Participant Flow

Patients were recruited from medical clinic between July 2010 and September 2011.

Participant milestones

Participant milestones
Measure	Arm I: Decitabine 0.2mg/kg INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	25
Overall Study Induction Phase	25
Overall Study Maintenance Phase	23
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I: Decitabine 0.2mg/kg INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Overall Study Death	1
Overall Study Physician Decision	1

Baseline Characteristics

Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I: Decitabine 0.2mg/kg n=25 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Age, Customized 40-49 years	1 participants n=5 Participants
Age, Customized 50-59 years	1 participants n=5 Participants
Age, Customized 60-69 years	8 participants n=5 Participants
Age, Customized 70-79 years	9 participants n=5 Participants
Age, Customized 80-89 years	6 participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants

PRIMARY outcome

Timeframe: Formal assessment at week 12 for study primary end-point (hematologic improvement).

Population: All patients enrolled and that received any treatment.

Outcome measures

Outcome measures
Measure	Arm I: Decitabine 0.2mg/kg n=25 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia Hematologic Improvement	7 participants
Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia Complete Remission	4 participants
Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia Partial Remission	0 participants
Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia Stable Disease	9 participants
Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia Disease Progression	5 participants

SECONDARY outcome

Timeframe: up to 12 months of treatment

Population: All patients that received treatment.

Incidence of treatment-emergent adverse events (AEs) will be presented in tables that include causality, seriousness, severity/grade, and whether the AE resulted in death or discontinuation of treatment, Laboratory data will be summarized in tables that show changes from pre-treatment values and frequencies of abnormal values. Descriptive statistics will also be provided.

Outcome measures

Outcome measures
Measure	Arm I: Decitabine 0.2mg/kg n=25 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Number of Patients That Experience > Grade 2 Non-hematologic Toxicity by National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) v4 Criteria	16 participants

SECONDARY outcome

Timeframe: at 12 months

Population: Patients that had cytogenetic abnormalities at baseline and were evaluable with follow-up metaphase karyotyping.

Described as the number of patients with a major cytogenetic response (refers to disappearance of a cytogenetic abnormality) or a minor cytogenetic response (50% or more reduction of abnormal metaphases).

Outcome measures

Outcome measures
Measure	Arm I: Decitabine 0.2mg/kg n=11 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Cytogenetic Response as Per IWG Criteria complete cytogenetic remission	5 participants
Cytogenetic Response as Per IWG Criteria partial cytogenetic remission	2 participants
Cytogenetic Response as Per IWG Criteria no cytogenetic remission	4 participants

SECONDARY outcome

Timeframe: 6 weeks after treatment

Population: All subjects that had treatment with DNMT1 depletion.

Evidence of pharmacodynamic effect will be correlated with clinical response criteria. The pharmacodynamic effect of treatment is defined as the number of participants that had depletion DNMT1 with minimal DNA damage and cytotoxicity.

Outcome measures

Outcome measures
Measure	Arm I: Decitabine 0.2mg/kg n=25 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Pharmacodynamic Evidence of Drug Effect.	25 participants

SECONDARY outcome

Timeframe: 6 weeks after treatment

Population: Patients with chromosomal abnormalities which were evaluable for follow-up karyotyping

Cytotoxicity is the ability to destroy cells. This will be measured by taking bone marrow samples and measuring the damage to cells. The level of cell destruction will be correlated with clinical response criteria.

Outcome measures

Outcome measures
Measure	Arm I: Decitabine 0.2mg/kg n=11 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Bone Marrow Evidence of Cytotoxicity. Complete cytogenetic remission	5 participants
Proportion of Patients With Bone Marrow Evidence of Cytotoxicity. Partial cytogenetic remission	2 participants

SECONDARY outcome

Timeframe: 6 weeks after treatment

Number of participants who, after therapy, had more of the differentiated types of blood (red cells, platelets, and white cells) compared to abnormal bone marrow cells than before therapy

Outcome measures

Outcome measures
Measure	Arm I: Decitabine 0.2mg/kg n=25 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Bone Marrow Evidence of Terminal Differentiation Response to Therapy.	11 participants

SECONDARY outcome

Timeframe: Baseline

Proportion of patients with particular genetic abnormalities, including DNA Methyltransferase 1 (DNMT1) depletion, detected by whole exome sequencing correlation with clinical response

Outcome measures

Outcome measures
Measure	Arm I: Decitabine 0.2mg/kg n=25 Participants INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Particular Genetic Abnormalities Detected by Whole Exome Sequencing Correlation With Clinical Response	4 participants

Adverse Events

Arm I

Serious events: 15 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Arm I n=25 participants at risk INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Vascular disorders Acute Left Popliteal DVT	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Respiratory, thoracic and mediastinal disorders aspiration pneumonia	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Infections and infestations bacterial infection	8.0% 2/25 • Number of events 2 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Metabolism and nutrition disorders Dehydration	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
General disorders Death	12.0% 3/25 • Number of events 3 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Blood and lymphatic system disorders Febrile neutropenia	40.0% 10/25 • Number of events 17 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
General disorders fever	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Skin and subcutaneous tissue disorders Furuncle on left groin area	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Nervous system disorders Headache	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Renal and urinary disorders Hematuria	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Vascular disorders Hypertension	4.0% 1/25 • Number of events 2 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Vascular disorders Hypotension	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
General disorders Left Sided Chest Pain	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Blood and lymphatic system disorders Neutropenic Fever	8.0% 2/25 • Number of events 4 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Vascular disorders Orthostasis	4.0% 1/25 • Number of events 2 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Vascular disorders Orthostatic Hypotension	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Infections and infestations Sepsis	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Infections and infestations Tooth Extraction	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.
Infections and infestations Urinary tract infection	4.0% 1/25 • Number of events 1 • Data collected from on treatment to completion of treatment over a 1 year period. Only grade 3 and above AEs were collected and all submitted as SAEs.

Other adverse events

Adverse event data not reported

Additional Information

Yogen Saunthararajah, MD

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Phone: 216-444-8170

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place