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A Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome

Primary Purpose

Myelodysplastic Syndrome

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

JNJ-30979754 15 mg/m2

JNJ-30979754 20 mg/m2

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring Myelodysplastic syndrome, MDS, Decitabine, JNJ-30979754

Eligibility Criteria

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

Inclusion Criteria:

Myelodysplastic syndrome (de novo or secondary) fitting any of the recognized French-American-British classifications: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia with white blood cells less than 13,000 /mm3
International Prognostic Scoring System (IPSS) greater than or equal to 0.5 (Intermediate-1, Intermediate-2 or high risk) by bone marrow assessment and bone marrow cytogenetics within 28 days before study registration
20 years or older
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Normal renal and hepatic function

Exclusion Criteria:

Acute Myeloid Leukemia (AML) with bone marrow blasts greater than or equal to 30%
Participants with a history of high-dose cytarabine (Ara-C) therapy (greater than 1,000 mg/m2/day)
Participants administered adrenal cortex hormones or anabolic hormones within 7 days of study initiation
Participants who have received a colony stimulating factor (CSF) formulation within 7 days of study initiation
Active double cancer
Uncontrolled cardiac disease or cognitive heart failure
Uncontrolled restrictive or obstructive pulmonary disease
Uncontrolled diabetes mellitus
Active viral or bacterial infection
Known positive serology for Human immunodeficiency virus

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Phase I: JNJ-30979754 15 mg/m2

Phase I: JNJ-30979754 20 mg/m2

Phase II: JNJ-30979754 20 mg/m2

Arm Description

JNJ-30979754 (decitabine) 15 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1

JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1

JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles

Outcomes

Primary Outcome Measures

Phase II: Overall Remission Rate (ORR): Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria (2000)

IWG response criteria (2000) - CR: bone marrow evaluations show < 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes.

Phase I and II: Number of Participants Who Experienced Adverse Events

Secondary Outcome Measures

Phase I: Maximum Observed Plasma Concentration of Decitabine (Cmax)

Phase I: Area Under the Plasma Concentration-time Curve (AUC)

Area under the curve from time zero to extrapolated infinite time (AUC Infinity) and area under the curve from time zero to last quantifiable concentration (AUC Last).

Phase I: Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000)

IWG response criteria (2000) - CR: bone marrow evaluations (mCR) show < 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia; PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes; HI: hemoglobin < 11 g/dL (erythroid); platelet < 100,000/mL; neutrophils < 1,000/mL.

Phase II: Median Time to Remission

Median time required for the participants to achieve remission (complete remission+partial remission).

Phase II: Median Time to Improvement

Median time required for the participants to achieve overall improvement (complete remission+partial remission+hematologic improvement)

Phase II: Median Duration of Remission

Median time duration for which participants achieved remission (complete remission+partial remission).

Phase II: Median Duration of Overall Improvement

Median time duration for which participants achieved overall improvement (complete remission+partial remission+hematologic improvement).

Phase II: Overall Improvement Rate: Number of Participants Who Achieved Complete Response (CR)+Partial Response (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000)

IWG response criteria (2000) - CR: bone marrow evaluations (mCR) show < 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes. HI: hemoglobin < 11 g/dL (erythroid); platelet < 100,000/mL; neutrophils < 1,000/mL.

Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial)

IWG 2000 - Major: disappearance of cytogenetic abnormality; Minor: 50% or more reduction in abnormal metaphases. IWG 2006 - Complete: disappearance of the chromosomal abnormality without appearance of new ones; Partial: At least 50% reduction of the chromosomal abnormality.

Full Information

NCT ID

NCT00796003

First Posted

November 20, 2008

Last Updated

October 10, 2013

Sponsor

Janssen Pharmaceutical K.K.

1. Study Identification

Unique Protocol Identification Number

NCT00796003

Brief Title

A Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome

Official Title

A Phase I/II Clinical Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

October 2013

Overall Recruitment Status

Completed

Study Start Date

July 2008 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Pharmaceutical K.K.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to to determine the recommended dose level of JNJ-30979754 (decitabine) as well as to assess the safety and effectiveness in patients with Myelodysplastic Syndrome (MDS).

Detailed Description

This is an open-label (both physician and patient know the name and dosage of drug), multi-center study. This study consists of two parts, Phase I and Phase II. In Phase I, approximately 9 participants will be enrolled ie, 3 participants for dose level 1 (15 mg/m2 of JNJ-30979754) and 6 participants for dose level 2 (20 mg/m2 of JNJ-30979754). Once the tolerability of 20 mg/m2 is confirmed additional 30 participants will be included to receive 20 mg/m2 and approximate total participants in Phase II will be 36. This study will include screening period (within 14 days prior to the day of initial administration of Cycle 1) and dosing period (1 cycle consists of administration of study medication for first 5 consecutive days + rested for 23 days; ie, total 28 days). Cycles will be reapeated in participants in whom decitabine was expected to be effective. Safety evaluations will include assessment of adverse events, vital signs, body weight, clinical laboratory tests: hematology, blood biochemistry and urinalysis, cardiopulmonary function tests: ECG, chest X ray and oximeter analysis.

6. Conditions and Keywords

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

Myelodysplastic Syndrome

Keywords

Myelodysplastic syndrome, MDS, Decitabine, JNJ-30979754

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase I: JNJ-30979754 15 mg/m2

Arm Type

Experimental

Arm Description

JNJ-30979754 (decitabine) 15 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1

Arm Title

Phase I: JNJ-30979754 20 mg/m2

Arm Type

Experimental

Arm Description

JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1

Arm Title

Phase II: JNJ-30979754 20 mg/m2

Arm Type

Experimental

Arm Description

JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles

Intervention Type

Drug

Intervention Name(s)

JNJ-30979754 15 mg/m2

Other Intervention Name(s)

decitabine

Intervention Description

JNJ-30979754 (decitabine) 15 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1.

Intervention Type

Drug

Intervention Name(s)

JNJ-30979754 20 mg/m2

Other Intervention Name(s)

decitabine

Intervention Description

Phase I: JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1. Phase II: JNJ-30979754 (decitabine) 20 mg/m2 will be administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles until the decitabine was expected to be effective in participants.

Primary Outcome Measure Information:

Title

Phase II: Overall Remission Rate (ORR): Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria (2000)

Description

Time Frame

Up to 1 years after the last participant enrolled

Title

Phase I and II: Number of Participants Who Experienced Adverse Events

Time Frame

Up to 1.5 years after the last participant enrolled

Secondary Outcome Measure Information:

Title

Phase I: Maximum Observed Plasma Concentration of Decitabine (Cmax)

Time Frame

Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1

Title

Phase I: Area Under the Plasma Concentration-time Curve (AUC)

Description

Area under the curve from time zero to extrapolated infinite time (AUC Infinity) and area under the curve from time zero to last quantifiable concentration (AUC Last).

Time Frame

Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1

Title

Phase I: Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000)

Description

Time Frame

Up to 28 Days of treatment Cycle 1

Title

Phase II: Median Time to Remission

Description

Median time required for the participants to achieve remission (complete remission+partial remission).

Time Frame

Up to 1.5 years after the last participant enrolled

Title

Phase II: Median Time to Improvement

Description

Median time required for the participants to achieve overall improvement (complete remission+partial remission+hematologic improvement)

Time Frame

Up to 1.5 years after the last participant enrolled

Title

Phase II: Median Duration of Remission

Description

Median time duration for which participants achieved remission (complete remission+partial remission).

Time Frame

Up to 1.5 years after the last participant enrolled

Title

Phase II: Median Duration of Overall Improvement

Description

Median time duration for which participants achieved overall improvement (complete remission+partial remission+hematologic improvement).

Time Frame

Up to 1.5 years after the last participant enrolled

Title

Description

IWG response criteria (2000) - CR: bone marrow evaluations (mCR) show < 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes. HI: hemoglobin < 11 g/dL (erythroid); platelet < 100,000/mL; neutrophils < 1,000/mL.

Time Frame

Up to 1.5 years after the last participant enrolled

Title

Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial)

Description

Time Frame

Up to 1.5 years after the last participant enrolled

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Myelodysplastic syndrome (de novo or secondary) fitting any of the recognized French-American-British classifications: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia with white blood cells less than 13,000 /mm3 International Prognostic Scoring System (IPSS) greater than or equal to 0.5 (Intermediate-1, Intermediate-2 or high risk) by bone marrow assessment and bone marrow cytogenetics within 28 days before study registration 20 years or older Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Normal renal and hepatic function Exclusion Criteria: Acute Myeloid Leukemia (AML) with bone marrow blasts greater than or equal to 30% Participants with a history of high-dose cytarabine (Ara-C) therapy (greater than 1,000 mg/m2/day) Participants administered adrenal cortex hormones or anabolic hormones within 7 days of study initiation Participants who have received a colony stimulating factor (CSF) formulation within 7 days of study initiation Active double cancer Uncontrolled cardiac disease or cognitive heart failure Uncontrolled restrictive or obstructive pulmonary disease Uncontrolled diabetes mellitus Active viral or bacterial infection Known positive serology for Human immunodeficiency virus

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Pharmaceutical K.K., Japan Clinical Trial

Organizational Affiliation

Janssen Pharmaceutical K.K.

Official's Role

Study Director

Facility Information:

City

Fukuoka

Country

Japan

City

Hamamatsu

Country

Japan

City

Hidaka

Country

Japan

City

Nagasaki

Country

Japan

City

Nagoya

Country

Japan

City

Shinjuku

Country

Japan

City

Tokyo

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

22816487

Citation

Oki Y, Kondo Y, Yamamoto K, Ogura M, Kasai M, Kobayashi Y, Watanabe T, Uike N, Ohyashiki K, Okamoto S, Ohnishi K, Tomita A, Miyazaki Y, Tohyama K, Mukai HY, Hotta T, Tomonaga M. Phase I/II study of decitabine in patients with myelodysplastic syndrome: a multi-center study in Japan. Cancer Sci. 2012 Oct;103(10):1839-47. doi: 10.1111/j.1349-7006.2012.02386.x. Epub 2012 Sep 14.

Results Reference

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A Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome

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