An Efficacy and Safety Study of Decitabine in Participants With Myelodysplastic Syndrome (MDS)

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

Decitabine

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring 5-aza-2'-deoxycytidine, decitabine, dacogen, Myelodysplastic Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants with documented pathological (bone marrow, no longer than 30 days before first dosing in study) evidence of Myelodysplastic syndromes (MDS) or of chronic myelomonocytic leukemia (CMML) by World health organisation classification
Participants with international prognostic scoring system (IPSS) score equal to 0.5 or more (only for participants for whom IPSS is applicable)
Participants with an Eastern oncology cooperative group (ECOG) performance status of 0-2
Participants with adequate hepatic (liver) and renal (kidney) function as measured by pre-treatment laboratory criteria within 21 days of starting treatment with decitabine
Participants must have recovered from toxic effects of previous therapy and not receiving any chemotherapy for a minimum of 4 weeks (6 weeks if the participants has been treated with a nitrosoureas) before to the first dose of study drug

Exclusion Criteria:

Participants with a diagnosis of acute myeloid leukemia (AML) (greater than 30 percent bone marrow blasts)
Participants with AML with multilineage dysplasia (abnormal development or cell growth) following MDS (20-30 percent bone marrow blasts) can be enrolled. For these latter participants an observation period of 1 month is necessary to exclude those participants with rapid progression to full blown AML
Participants with previous treatment with azacitadine or decitabine or hematopoietic stem cell transplantation less than 1 year prior to study enrollment
Participants with past history of malignancy and received any treatment for this before malignancy within the last 3 years, except for superficial bladder cancer, basal cell or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia (CIN) or prostate intraepithelial neoplasia (PIN)
Participants with known hepatitis B (surface antigen-positive) or active hepatitis C infection

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Decitabine

Arm Description

Decitabine 20 milligram per square meter (mg per m^2) will be administered intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 1 hour, once daily for 5 consecutive days of a 28 days cycle up to 8 cycles or continued until disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Percentage of Participants With Response

Percentage of participants with response: complete response (CR) or partial response (PR) according to International Working Group (IWG) 2006 criteria was evaluated. CR in bone marrow is defined as<=to 5% myeloblasts with normal maturation of all cell lines and persistent dysplasia was noted in peripheral blood hemoglobin >=11 gram (g) per deciliter (dl), platelets >=100*10^9 liter (l), neutrophils >=1.0*10^9 l, Blasts 0%. Partial response is defined as all CR criteria if abnormal before treatment except: bone marrow blasts decreased by >=50% over pre-treatment but still >=5%.

Secondary Outcome Measures

Percentage of Participants With Hematologic Treatment Response

Hematologic treatment response was assessed as per IWG 2006 criteria. This is measured in erythroid(HI-E), platelet(HI-P) and neutrophil(HI-N) lineages. HI-E response(pre-treatment<11 gram per deciliter [g/dl]):hemoglobin increase by>=1.5 g/dl and relevant reduction in RBC transfusions by 4 RBC transfusions/8week. HI-P response (pre-treatment<100*109/l):absolute increase of >=30*10^9/l for participants starting with>20*10^9/l and increase from <20*10^9/l to>20*10^9/l and by at least 100%. HI-N response (pre-treatment<1.0*10^9/l): at least 100% increase and an absolute increase >0.5*10^9/l.

Percentage of Participants With Cytogenetic Response

Cytogenetic responses was assessed as per IWG 2006 criteria which define complete response as disappearance of the chromosomal abnormality without appearance of new ones and partial response as at least 50 percent reduction of the chromosomal abnormality.

Time to Acute Myeloid Leukemia (AML) Progression or Death

Time to AML is defined as greater than 30 percent of blasts in bone marrow or the time to death was calculated from the date of treatment start until disease progression to AML or until death, which ever occurred first. Participants who were still alive and did not progress to AML were censored at the moment of last visit.

Overall Survival

Overall survival was defined as the time from the date of treatment start until death (whatever the cause). It was calculated from Kaplan-Meier estimates. Participants still alive were censored at the moment of last visit or contact.

Percentage of Participants With Transfusion Dependency

Transfusion requirements for both red blood cells as well as platelets were recorded for each participant.

Percentage of Participants With Transfusion Independency

Transfusion independent participants were calculated from all the participants who required transfusion in the duration of 8 weeks before first dose until disease progression or death or up to 736 days. Transfusion independence was defined as lack of requirement for transfusions for at least 8 weeks.

Duration for Hospitalization

Duration of hospitalization was calculated for each participant, using the sum of all hospital days by subtracting the date of discharge from the date of admission.

Number of Events Which Led to Hospitalization

The events (reasons) for hospitalizations such as infection, transfusion, acute choleycystitis, allergic transfusion reaction, dyspnoea with right pleural effusion, febrile neutropenia, fever, for decitabine, Myelodysplastic Syndrome (MDS) hematuria, paronychia, pneumonia, heart failure, peri-anal abscess (PAA), pancytopenia,fluctuated neutropenia fever, right dorsal foot cellulitis, Right lower (Rt.Lw) lung pneumonia with impending respiratory (resp) failure, Serious adverse event (SAE)+schedule hospitalization for decitabine, septic shock and not available were reported.

Quality of Life Assessment

The quality of life was assessed by the questionnaire QLQ C-30 designed by European Organization for the Research and Treatment of Cancer (EORTC). EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Most questions used 4-point scale (1=Not at All' to 4=Very Much') and 2 questions: Q29 on overall health and Q30 on overall quality of life uses 7-point scale ranging from 1=Very Poor to 7=Excellent. Higher score indicates better quality of life.

Full Information

NCT ID

NCT00744757

First Posted

August 29, 2008

Last Updated

August 26, 2013

Sponsor

Johnson & Johnson Taiwan Ltd

1. Study Identification

Unique Protocol Identification Number

NCT00744757

Brief Title

An Efficacy and Safety Study of Decitabine in Participants With Myelodysplastic Syndrome (MDS)

Official Title

A Phase II Multi-center Study of 5-AZA-2'-Deoxycytidine (Decitabine) Single Agent in Taiwanese Patients With Myelodysplastic Syndrome (MDS)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

August 2008 (undefined)

Primary Completion Date

September 2010 (Actual)

Study Completion Date

August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johnson & Johnson Taiwan Ltd

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this study is to evaluate the response rate of decitabine in previously treated and untreated Taiwanese participants with Myelodysplastic Syndrome (MDS - a disease associated with decreased production of blood cells, blood cells are produced but do not mature normally).

Detailed Description

This is an open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, "unblinded"), multi-center (when more than 1 hospital or medical school team work on a medical research study), single-arm study of decitabine. The study will consist of 5 phases: Pre-treatment phase (before 30 days of first dose), Treatment phase (consist of 8 cycles, each cycle of 28 days), End-of-treatment phase (consist of 30-42 days after the last dose of cycle 8, or at time of discontinuation), Extension phase (1 cycle of 4 weeks) and Post-study phase or follow-up phase (every 2 months until 1 year, lost to follow-up or death). Participants who achieve a complete remission (when a medical problem gets better or goes away at least for a while) will be treated for at least 2 more cycles after first documentation of complete response (CR), after which treatment can be discontinued. Decitabine in a dose of 20 milligram per square meter (mg per m^2) will be administered intravenously over 1 hour infusion, 1 hour, once daily for 5 consecutive days of a 28 days cycle up to 8 cycles or continued until disease progression or unacceptable toxicity. The primary objective is to evaluate the best response rate (complete response and partial response). Participants' safety will be monitored throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndrome

Keywords

5-aza-2'-deoxycytidine, decitabine, dacogen, Myelodysplastic Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Decitabine

Arm Type

Experimental

Arm Description

Decitabine 20 milligram per square meter (mg per m^2) will be administered intravenous (into a vein) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 1 hour, once daily for 5 consecutive days of a 28 days cycle up to 8 cycles or continued until disease progression or unacceptable toxicity.

Intervention Type

Drug

Intervention Name(s)

Decitabine

Other Intervention Name(s)

Dacogen, 5-aza-2'-deoxycytidine

Intervention Description

Decitabine 20 mg per m^2 will be administered intravenous infusion over 1 hour, once daily for 5 consecutive days of a 28 days cycle up to 8 cycles or continued until disease progression or unacceptable toxicity.

Primary Outcome Measure Information:

Title

Percentage of Participants With Response

Description

Percentage of participants with response: complete response (CR) or partial response (PR) according to International Working Group (IWG) 2006 criteria was evaluated. CR in bone marrow is defined as<=to 5% myeloblasts with normal maturation of all cell lines and persistent dysplasia was noted in peripheral blood hemoglobin >=11 gram (g) per deciliter (dl), platelets >=100*10^9 liter (l), neutrophils >=1.0*10^9 l, Blasts 0%. Partial response is defined as all CR criteria if abnormal before treatment except: bone marrow blasts decreased by >=50% over pre-treatment but still >=5%.

Time Frame

Day 1 of Cycle 2, 4, 6, 8; each Cycle of 28 days and End of treatment (30-42 days after Cycle 8 or early withdrawal)

Secondary Outcome Measure Information:

Title

Percentage of Participants With Hematologic Treatment Response

Description

Hematologic treatment response was assessed as per IWG 2006 criteria. This is measured in erythroid(HI-E), platelet(HI-P) and neutrophil(HI-N) lineages. HI-E response(pre-treatment<11 gram per deciliter [g/dl]):hemoglobin increase by>=1.5 g/dl and relevant reduction in RBC transfusions by 4 RBC transfusions/8week. HI-P response (pre-treatment<100*109/l):absolute increase of >=30*10^9/l for participants starting with>20*10^9/l and increase from <20*10^9/l to>20*10^9/l and by at least 100%. HI-N response (pre-treatment<1.0*10^9/l): at least 100% increase and an absolute increase >0.5*10^9/l.

Time Frame

Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7 and 8, each Cycle of 28 days and End of treatment (30-42 days after Cycle 8 or early withdrawal)

Title

Percentage of Participants With Cytogenetic Response

Description

Cytogenetic responses was assessed as per IWG 2006 criteria which define complete response as disappearance of the chromosomal abnormality without appearance of new ones and partial response as at least 50 percent reduction of the chromosomal abnormality.

Time Frame

Day 1 of Cycle 2, 4, 6, 8; each Cycle of 28 days and End of treatment (30-42 days after Cycle 8 or early withdrawal)

Title

Time to Acute Myeloid Leukemia (AML) Progression or Death

Description

Time to AML is defined as greater than 30 percent of blasts in bone marrow or the time to death was calculated from the date of treatment start until disease progression to AML or until death, which ever occurred first. Participants who were still alive and did not progress to AML were censored at the moment of last visit.

Time Frame

Start of treatment until disease progression or death (whichever occur first) or up to 736 days

Title

Overall Survival

Description

Overall survival was defined as the time from the date of treatment start until death (whatever the cause). It was calculated from Kaplan-Meier estimates. Participants still alive were censored at the moment of last visit or contact.

Time Frame

Start of treatment until disease progression or death (whichever occur first) or up to 736 days

Title

Percentage of Participants With Transfusion Dependency

Description

Transfusion requirements for both red blood cells as well as platelets were recorded for each participant.

Time Frame

8 weeks before first dose until disease progression or death (whichever occur first) or up to 736 days

Title

Percentage of Participants With Transfusion Independency

Description

Transfusion independent participants were calculated from all the participants who required transfusion in the duration of 8 weeks before first dose until disease progression or death or up to 736 days. Transfusion independence was defined as lack of requirement for transfusions for at least 8 weeks.

Time Frame

8 weeks before first dose and 736 days of treatment

Title

Duration for Hospitalization

Description

Duration of hospitalization was calculated for each participant, using the sum of all hospital days by subtracting the date of discharge from the date of admission.

Time Frame

Cycle 1 up to Cycle 8, each cycle of 28 days.

Title

Number of Events Which Led to Hospitalization

Description

The events (reasons) for hospitalizations such as infection, transfusion, acute choleycystitis, allergic transfusion reaction, dyspnoea with right pleural effusion, febrile neutropenia, fever, for decitabine, Myelodysplastic Syndrome (MDS) hematuria, paronychia, pneumonia, heart failure, peri-anal abscess (PAA), pancytopenia,fluctuated neutropenia fever, right dorsal foot cellulitis, Right lower (Rt.Lw) lung pneumonia with impending respiratory (resp) failure, Serious adverse event (SAE)+schedule hospitalization for decitabine, septic shock and not available were reported.

Time Frame

Start of treatment until disease progression or death or up to Cycle 8, each cycle of 28 days

Title

Quality of Life Assessment

Description

The quality of life was assessed by the questionnaire QLQ C-30 designed by European Organization for the Research and Treatment of Cancer (EORTC). EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer participants. Most questions used 4-point scale (1=Not at All' to 4=Very Much') and 2 questions: Q29 on overall health and Q30 on overall quality of life uses 7-point scale ranging from 1=Very Poor to 7=Excellent. Higher score indicates better quality of life.

Time Frame

Day 1 of Cycle 1 and Cycle 8 (each cycle of 28 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Participants with documented pathological (bone marrow, no longer than 30 days before first dosing in study) evidence of Myelodysplastic syndromes (MDS) or of chronic myelomonocytic leukemia (CMML) by World health organisation classification Participants with international prognostic scoring system (IPSS) score equal to 0.5 or more (only for participants for whom IPSS is applicable) Participants with an Eastern oncology cooperative group (ECOG) performance status of 0-2 Participants with adequate hepatic (liver) and renal (kidney) function as measured by pre-treatment laboratory criteria within 21 days of starting treatment with decitabine Participants must have recovered from toxic effects of previous therapy and not receiving any chemotherapy for a minimum of 4 weeks (6 weeks if the participants has been treated with a nitrosoureas) before to the first dose of study drug Exclusion Criteria: Participants with a diagnosis of acute myeloid leukemia (AML) (greater than 30 percent bone marrow blasts) Participants with AML with multilineage dysplasia (abnormal development or cell growth) following MDS (20-30 percent bone marrow blasts) can be enrolled. For these latter participants an observation period of 1 month is necessary to exclude those participants with rapid progression to full blown AML Participants with previous treatment with azacitadine or decitabine or hematopoietic stem cell transplantation less than 1 year prior to study enrollment Participants with past history of malignancy and received any treatment for this before malignancy within the last 3 years, except for superficial bladder cancer, basal cell or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia (CIN) or prostate intraepithelial neoplasia (PIN) Participants with known hepatitis B (surface antigen-positive) or active hepatitis C infection

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Johnson & Johnson Taiwan, Ltd. Clinical Trial

Organizational Affiliation

Johnson & Johnson Taiwan Ltd

Official's Role

Study Director

Facility Information:

City

Changhua

Country

Taiwan

City

Kaohsiung

Country

Taiwan

City

Taichung

Country

Taiwan

City

Tainan

Country

Taiwan

City

Taipei

Country

Taiwan

City

Tau-Yuan County 333

Country

Taiwan

Myelodysplastic Syndrome

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial