Clinical trial NCT00796003: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myelodysplastic Syndrome
Keywords: Myelodysplastic syndrome
MDS
Decitabine
JNJ-30979754
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2008-11-24
Enrollment: 39
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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)
timeFrame: Up to 1 years after the last participant enrolled
measure: Phase I and II: Number of Participants Who Experienced Adverse Events
timeFrame: Up to 1.5 years after the last participant enrolled
Secondary outcomes:
measure: Phase I: Maximum Observed Plasma Concentration of Decitabine (Cmax)
timeFrame: 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
measure: Phase I: Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: 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
measure: 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)
timeFrame: Up to 28 Days of treatment Cycle 1
measure: Phase II: Median Time to Remission
timeFrame: Up to 1.5 years after the last participant enrolled
measure: Phase II: Median Time to Improvement
timeFrame: Up to 1.5 years after the last participant enrolled
measure: Phase II: Median Duration of Remission
timeFrame: Up to 1.5 years after the last participant enrolled
measure: Phase II: Median Duration of Overall Improvement
timeFrame: Up to 1.5 years after the last participant enrolled
measure: 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)
timeFrame: Up to 1.5 years after the last participant enrolled
measure: Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial)
timeFrame: Up to 1.5 years after the last participant enrolled
Other outcomes:
Locations:
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
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References:
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.